Classic Kaposi's Sarcoma Research Articles

Prevalence of Toscana and Sicilian Phlebovirus Antibodies in Classic Kaposi Sarcoma Case Patients and Control Subjects in Sicily

To assess whether arthropod bites promote Kaposi sarcoma (KS), we determined the seroprevalence of Sicilian (SFSV) and Toscana (TOSV) phlebovirus antibodies in 30 patients with classic KS and 100 controls in Sicily. Nine (6.9%) subjects, all controls, were positive for SFSV, whereas 41 (31.5%) were positive for TOSV. Seroprevalence with immunoglobulin (Ig) M or IgG against either virus was significantly higher in controls (43% vs 13.3% in case patients; P < .01). Adjusted for age, IgG seroprevalence was significantly lower in KS patients compared to controls (adjusted odds ratio, 0.22; 95% confidence interval, .07-.72). Low phlebovirus seroprevalence in patients with KS may reflect incapacity to produce robust, persistent antibody responses, and suggests that arthropod bites do not promote KS.

Molecular epidemiology of human herpesvirus 8 variants in Kaposi's sarcoma from Iranian patients

Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological and molecular information about HHV-8 variants circulating among the Iranian population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS biopsies from Iranian patients mainly affected by classic KS. DNA samples were subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K, respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out of 41) fall into the large C clade with only 2 belonging to the A clade. In conclusion, HHV-8 variants identified among classic Iranian KS are largely related to Eurasian genotypes previously identified in KS from Mediterranean, Middle East, and East Asian regions.

The Palliative Radiotherapy of Classic Kaposi’s Sarcoma of Foot Region: Retrospective Evaluation

The life quality of the patients with classic Kaposi's sarcoma exit in the foot region (toes, dorsum pedis, plantar pedis and region calcaneus) were impaired due to the walking or the pain while wearing shoes. The widely used radiotherapy in this patient group is applied with different doses and fractionation schemes. The data is limited for evaluating response and to- xicity of radiation to optimized radiotherapy techniques of foot' CKS. The aim of the study was to assess the effectiveness and safety of RT for these patients. Thirty-one therapy areas of 15 patients with histological confirmed Kaposi's sarcoma in the foot region and treated between 1999 and 2005 were evaluated retrospectively. The male/female ratio was 2.75/1 and the median age was 63 years of age. The most frequently used radiotherapy scheme was 3000cGy in 10 fractions. The median follow-up time was 68.4 months. The complete response ratios were 86.7%, 93.3%, 93.3% for 30 therapy are- as at 6, 12 months and 5 years, consecutively. Acute complications were observed in 17 (54.8%) therapy areas. All side ef- fects developed due to the therapy were controlled with supportive treatment. Normal foot movements were ensured wit- hin 2-4 weeks after the radiotherapy. According to our results, the radiotherapy is effective and safe therapy modality for Ka- posi's sarcoma of the foot region. However, the first response to radiation is usually frustrating and it may increase the pa- tients' complaint about the foot due to the acute toxicity. This can be improved completely with supportive therapy.

Differences in Kaposi sarcoma‐associated herpesvirus‐specific and herpesvirus‐non‐specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily

Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution.

Prevalence of antibodies against Kaposi's sarcoma associated herpes virus (KSHV) complement inhibitory protein (KCP) in KSHV-related diseases and their correlation with clinical parameters

Kaposi's sarcoma-associated herpes virus (KSHV) encodes its own inhibitor of the complement system, designated KSHV complement control protein (KCP). Previously, we detected anti-KCP antibodies in a small group of 22 patients suffering from Kaposi's sarcoma (KS) and KSHV-related lymphoproliferative diseases (Vaccine, 25:8102-9). Anti-KCP antibodies were more prevalent in individuals suffering from KSHV-related lymphomas than KS and also in those with high titer of antibodies against lytic KSHV antigens. Herein we analyze anti-KCP antibodies in 175 individuals originating from three different groups from northern Sweden or Italy, which included patients suffering from classical or HIV-associated KS, Multicentric Castleman's Disease, KSHV-associated solid lymphoma, pleural effusion lymphoma and healthy individuals with detectable KSHV immune response. Our current study confirmed previous observations concerning antibody prevalence but we also analyzed correlations between anti-KCP antibodies and classical KS evolution, clinical stage and viral load in body fluids. Furthermore, we show that patient's anti-KCP antibodies are able to decrease the ability of KCP to inhibit complement. This fact combined with results of statistical analysis suggests that KCP inactivation by specific antibodies may influence progression of classical KS.

Bilateral Tonsillar and Esophageal Kaposi Sarcoma in an HIV-Negative Patient

Tonsillar involvement in Kaposi sarcoma is extremely rare, as only a few such cases have been reported; all but 1 of these previously reported cases occurred in patients with human immunodeficiency virus (HIV) infection. We describe what to the best of our knowledge is the first reported case of concurrent bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient. A 68-year-old man presented with sore throat and dysphagia. Clinical examination revealed the presence of bilateral and asymmetrical tonsillar masses, as well as generalized lymphadenopathy in the cervical chain. The masses were resected, and findings on histopathologic analysis were consistent with Kaposi sarcoma. In addition, human herpesvirus 8 was demonstrated on a tonsil specimen by polymerase chain reaction, and microinvasive squamous cell carcinoma was also detected. Later, another Kaposi sarcoma lesion was detected in the lower third of the esophagus. We recommend that clinicians not discount the possibility of oral classic Kaposi sarcoma in the workup of an immunocompetent patient with oral vascular lesions.

SU-E-T-480: Classic Kaposiˈs Sarcoma at Lower-Extremity Irradiation with Helical Tomotherapy

Purpose: To spare parts of the lymphatic drainage, muscle and skeleton of the lower extremities, a treatment technique using a helical tomotherapy (HT) for Classic Kaposi's sarcoma (KS) was developed and the analysis of surface doses around the lesion was performed. Methods: To achieve a homogenous dose distribution over the surface of the lower extremity, the gaps between the toes of the foot of a patient were packed by a thermal plastic material (poly‐flex II). For more effective immobilization and precise localization, the poly‐flex II‐covering foot mold was enclosed by the water‐ equivalent wax shaped into a brick and marked the localization (wax‐mold). A treatment planningCT of the patient with the custom‐made wax‐poly‐flex II brick was taken. CTV was contoured around the lesion surface with at least 0.5 cm depth. The PTV was created by expanding an isotropic 0.5 cm margin from CTV. A core structure spaced with 0.5 cm from PTV was contoured and assigned as a constraint to achieve steep dose gradient at shallow region. A prescribed dose (Dp) of 37.5 Gy in 15 fractions with a field width of 2.5 cm and a pitch of 0.287 were used for Tomotherapy Hi Art Planning system. MVCT image registration was performed before daily treatment. The surface doses around the lesions were measured by EBT2 films. Results: The 95% of Dp was received by at least 95% of PTV, and the maximum dose was less than 110% of Dp. The dose distribution in the central core fell off steeply with the mean dose of 50% of Dp. The measured doses were 94 to 99% of Dp. Conclusions: Combined with the image‐guided HT and wax‐mold device, an adequate doses to the skin can be achieved and the doses to the normal structures can be reduced significantly for KS at lower‐extremity irradiation.

Multicentric phase II clinical trial evaluating the role of everolimus (RAD001) in endemic or classic Kaposi’s sarcoma (C06-46).

10067 Background: Classic Kaposi’s sarcoma (CKS) is an angioproliferation associated with human herpes virus 8 (HHV8), which sometimes requires systemic treatment. Rapamycin and everolimus are mTOR...

Virological and molecular characterization of Kaposi’s sarcoma-associated herpesvirus strains from Xinjiang, China

Kaposi's sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion affecting the skin. KS-associated herpesvirus (KSHV/HHV-8) is etiologically linked to all epidemiological forms of KS. However, clinical phenotypes show considerable discrepancy, indicating the presence of virological and molecular characteristics of KSHV that influence its pathogenesis. We investigated the molecular virological features of KSHV strains from Xinjiang, where KSHV infection is endemic and there is a high incidence of KS. Phylogenetic characterization based on the VR1 region of the KSHV K1 gene for 21 classical and AIDS-KS specimens revealed the Eurasian KSHV genotypes C (n = 18) and A (n = 3), with subtypes A5, C6, and C7 identified for the first time in China. The distribution was closely associated with their unique ethnic origin and evolution. The KSHV viral load in AIDS-KS was substantially lower than in classic KS (p = 0.05), as quantified by real-time fluorescent quantitative polymerase chain reaction (PCR). The results reveal the general consistency of the biological and pathological properties of local KS with others, but characteristics associated with unique ethnicity evolution still remain.

Intralesional vincristine combined with cryotherapy for recalcitrant verrucas

Verrucas are often recalcitrant to conventional cryotherapy. Since 1970, intralesional bleomycin has been used off-label by dermatologists. But in some cases, the results of intralesional bleomycin were disappointing. Vincristine is a well-known vinca alkaloid antiblastic drug that has been used for treating hematological neoplasm and nephroblastomas. It was reported good efficacy of intralesional vincristine for treating nodular lesion in classic Kaposi sarcoma. Its use in epithelial neoplasm and Kaposi sarcoma may support its efficacy in recalcitrant verrucas. The three patients selected for the study presented severe verrucas on foot, and they had already undergone cryotherapy several times and there was no improvement. They got intralesional vincristine injection on their verrucas. The target lesion was infiltrated with 0.03 mL of vincristine sulphate at a concentration of 1 µg/mL. The injected amount of vincristine was proportional to the diameter of the nodule. After two treatments had been completed, there was a great decrease of lesion size compared with the other lesions. The three patients complained of pain lasting for several days. This pain was generally well tolerated. Intralesional vincristine injection on verruca is an effective and rapid novel method, and when combined with cryotherapy, shows excellent therapeutic response.

Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran

Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi's sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

Successful treatment of classic Kaposi sarcoma with low-dose intramuscular immunoglobulins

Successful treatment of classic Kaposi sarcoma with low-dose intramuscular immunoglobulins

Pilot Study of Oral Valganciclovir Therapy in Patients With Classic Kaposi Sarcoma

We conducted a clinical trial of oral valganciclovir, a drug with in vitro activity against Kaposi sarcoma (KS)-associated herpesvirus (KSHV), in classic KS. Five human immunodeficiency virus-seronegative participants received valganciclovir for up to six 4-week cycles at doses used for cytomegalovirus infection. None of the study subjects showed an objective response; KS progressed in 4 subjects after 1-4 cycles and remained stable in 1 subject after 6 cycles. KS biopsies showed minimal lytic KSHV antigen and gene expression at baseline and no treatment-associated changes. Although valganciclovir was not active against KS in this setting, other appropriately targeted anti-herpesviral strategies may prove to be more effective.

AIDS-Kaposi Sarcoma and Classic Kaposi Sarcoma: are different ultrasound patterns related to different variants?

BackgroundKaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease.MethodsCutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern.ResultsThe B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B).ConclusionsOur preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.

Non-AIDS Associated Kaposi's Sarcoma: Clinical Features and Treatment Outcome

BackgroundKaposi's sarcoma (KS) in HIV negative patients is rare and has to be distinguished from AIDS associated KS. Two groups are at risk to develop non-AIDS related KS: elderly men mainly of Mediterranean origin and persons with iatrogenic immunosuppression.Patients and MethodsIn order to define risk-groups and major clinical features we retrospectively evaluated clinical data of all patients with non-AIDS associated KS presenting to the Department of Dermatology, University Hospital Tuebingen between 1987 and 2009. Data were extracted from the tumor registry of the Comprehensive Cancer Center Tuebingen and from patient records.Results20 patients with non-AIDS KS have been identified. The average age at KS onset was 66.6 years; the male-to-female-ratio was 3∶1. Most of the patients were immigrants from Mediterranean or Eastern European countries (60%). 15 cases of classic KS versus 5 cases of iatrogenic KS were observed. In 95% of the cases, KS was limited to the skin, without mucosal, lymph node or visceral manifestation. KS lesions were in all cases multiple and mostly bilateral, the most common localization was the skin of the lower extremities. Tumor control was achieved in nearly all cases by the use of local or systemic therapy. No patient died from KS.ConclusionsUnlike KS in AIDS patients, non-AIDS associated KS is a rather localized process which rarely involves lymph nodes or organs. It is mostly seen in elderly males from Mediterranean or Eastern European countries and in most cases responsive on local or systemic therapeutic strategies.

Lymphatic Differentiation in Classic Kaposi’s Sarcoma: Patterns of D2-40 Immunoexpression in the Course of Tumor Progression

The recent development of lymphatic endothelium-specific immuno-indicators has given rise to research on the histogenesis of Kaposi sarcoma (KS), specifically focusing on its lymphatic root and differentiation. D2-40 is a new lymphatic marker that recognizes podoplanin and is easily applied to formalin-fixed paraffin-embedded human tissues. This study examined D2-40 immunoexpression in 178 classical KS lesions using immunohistochemical methods. D2-40 immunoexpression was also examined in 63 non-KS soft tissue lesions to test the reliability of D2-40 monoclonal antibody in the pathological diagnosis of KS. D2-40 immunoreactivity was detected at all of the KS lesions and in lymphangioma and nonneoplastic lymphatic endothelium. There was no significant relationship between the extent of D2-40 staining and histopathological stage; however, there was a positive correlation between the staining intensity and histopathological stage in KS cases. D2-40 immunoreactivity was detected at all histopathological stages of KS and may be added to the routine immunohistochemical panel used for the differential diagnosis of KS. Widespread D2-40 protein expression is evidence of a lymphatic origin or the differentiation of neoplastic cells in KS, and D2-40 expression increases with tumor progression.

Treatment of a Large Classic Kaposi Sarcoma Using High-Dose-Rate Brachytherapy and 3D Planning for Volume Treatment Optimization

Treatment of a Large Classic Kaposi Sarcoma Using High-Dose-Rate Brachytherapy and 3D Planning for Volume Treatment Optimization

Classic Kaposi sarcoma mimicking chilblains

Kaposi Sarcoma (KS) is a low-grade vascular tumor associated with human herpes virus-8 infection. It usually presents in elderly patients as violaceous plaques of the lower limbs. However, KS may present in a wide spectrum of atypical clinical forms, leading to misdiagnoses. We report a case of classic KS mimicking chilblains.

Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls

Background:Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg.Methods:Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site.Results:Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (−2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07).Conclusion:KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy.

Classic Kaposi sarcoma treated with topic imiquimod: One case report and review

Classic Kaposi sarcoma treated with topic imiquimod: One case report and review