Concurrent development of HIV-negative Kaposi's sarcoma and mycosis fungoides in an elderly Inuit from Canada.

An 88-year-old Inuit man from Northern Canada presented with an extensive skin rash associated with numerous violaceous skin nodules on his palms and lower extremities. Biopsy of a skin nodule revealed Kaposi's sarcoma (KS), a human herpesvirus 8 (HHV8)-associated malignancy, whereas biopsy of the erythematous skin showed an atypical infiltrate of CD4-positive T-cells that, together with TCR gene rearrangement and presence of clonal T-cells in peripheral blood by flow cytometry, was consistent with a T-cell lymphoma, mycosis fungoides (MF) subtype. Serology was negative for HIV and HTLV-I/II and no immunodeficiency syndrome was identified. The patient was successfully treated with an oral retinoid for KS, and with topical hydrocortisone and ultraviolet B (UVB) phototherapy for MF. This case highlights the existence of HHV8-related lesions in native persons of Northern Canada, and also that MF-induced immunosuppression combined with immunosenescence may play a role in the development of non-HIV-related KS.

Social behavioral correlates of Kaposi sarcoma-associated herpesvirus infection among Han and Uygur populations in Xinjiang, China.

BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is endemic in Xinjiang, China and its prevalence varies considerably across ethnic groups. The current study explored the prevalence and correlates of KSHV infection among Han and Uygur populations in Xinjiang. METHODS: A cross-sectional study, including 282 Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants underwent face to face questionnaire interview. Plasma samples were collected and screened for KSHV infection using immunofluorescence assay. Univariate and multivariate analyses were conducted to examine the correlates of KSHV seropositivity. RESULTS: The KSHV seroprevalence was 41.6% (95% confidence interval [CI], 37.6-45.6) overall and was higher in the Uygur group (59.9%; 95% CI, 54.3-65.4) than the Han group (21.3%; 95% CI, 16.6-26.5). A significant difference in the geometric mean titer (GMT) of the KSHV antibodies was detected between the Uygur and Han groups (158.2; interquartile range [IQR], 80-320 vs 89.1; IQR, 40-160; P < 0.001). After adjusting for potential confounders, Uygur ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05-8.90), age greater than or equal to 50 years (OR, 1.84; 95% CI, 1.24-2.77), and preference for meat diet (OR, 2.15; 95% CI, 1.05-4.46) were significantly associated with increased odds of KSHV seropositivity. CONCLUSION: The study demonstrated high prevalence and correlates of KSHV infection in both Han and Uygur populations in Xinjiang, China. There is an urgent need for programmatic adaptation to address primary prevention interventions of KSHV infection in this endemic region.

Ultraviolet Radiation and Kaposi Sarcoma Incidence in a Nationwide US Cohort of HIV-Infected Men.

Background: Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression. All statistical tests were two-sided. Results: Based on discharge records, there were 422 newly diagnosed KS cases among 17 597 HIV-infected veterans. Cohort members with prior NMSC had a statistically significantly increased risk of KS (HR = 8.64, 95% CI = 6.23 to 11.96) in the total population. Risk of KS was higher for quartile 4 vs 1 among the total population (HR = 1.49, 95% CI = 1.02 to 2.16, Ptrend UVR quartile [coded 1 to 4] = .02) and among whites (HR = 1.75, 95% CI = 1.11 to 2.78, Ptrend = .009), but not among African Americans (HR = 1.23, 95% CI = 0.71 to 2.15, Ptrend = .23). Conclusions: KS risk was elevated among HIV-infected men with NMSC diagnosis and in those living in locations with high ambient UVR at time of HIV diagnosis. Our novel findings suggesting that UVR exposure may increase KS risk warrant further investigation.

A case of Kaposi sarcoma in an immunocompetent, heterosexual Irish man: a discussion of etiology and viral transmission.

Four types of Kaposi sarcoma (KS) have been described, all of which are caused by human herpesvirus-8 (HHV-8).  The incidence of KS in the United States is highest among HIV-positive homosexual men and elderly men of Eastern European, Jewish, or Mediterranean descent. However, few reports describe KS in HIV-negative, immunocompetent heterosexual men in the United States. HHV-8 is transmitted largely via saliva and close sexual contact, whereas there are only a handful of reports of transmission via blood and blood products. We report a case of an HIV-negative, immunocompetent heterosexual man who acquired KS via blood transfusion. A 77-year-old immunocompetent, monogamously heterosexual, HIV-negative Irish man presented with a biopsy-proven KS lesion on the right thigh. Past surgical history included a coronary artery bypass graft, during which he received a blood transfusion from an unknown donor source.  His ecchymotic KS lesions progressed while on doxycycline, intralesional vinblastine, and topical anti-angiogenic medications.  The patient eventually achieved stabilization of KS lesions with acitretin. Our case report emphasizes the need to characterize the phenotype and transmission route of HHV-8 in heterosexual, immunocompetent patients in geographic regions with low HHV-8 seroprevalence.

Mitochondrial haplogroups and control region polymorphisms in Kaposi's sarcoma patients.

Inflammation and reactive oxygen species (ROS) production have recently considered as key mechanisms in the pathogenesis of Kaposi's sarcoma (KS). Since mitochondria are the major source of ROS production, this organelle may play a main role in KS development. However, there are no studies on mtDNA variations and haplogroups in this area. The focus of this study was to investigate the mtDNA variants and haplogroups in KS patients and their relationship to tumor development. To address this, we have genotyped mtDNA in 45 Iranian KS patients and 48 age and sex-matched Iranian controls. A strong positive correlation was observed between UK cluster and decreased risk of KS. Our results suggest that the UK cluster might be a protective haplogroup for KS development. It is probably superhaplogroup UK, with lower ATP and ROS production, may prevent KSHV reactivation from latent to lytic phase that is essential for KS development.

Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.

Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

Genotypic analysis of Kaposi's sarcoma-associated herpesvirus from patients with Kaposi's sarcoma in Xinjiang, China.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of all forms of Kaposi's sarcoma (KS), including AIDS-KS, endemic KS, classic KS and iatrogenic KS. Based on Open reading frame (ORF) K1 sequence analysis, KSHV has been classified into seven major molecular subtypes (A, B, C, D, E, F and Z). The distribution of KSHV strains varies according to geography and ethnicity. Xinjiang is a unique region where the seroprevalence of KSHV is significantly higher than other parts of China. The genotyping of KSHV strains in this region has not been thoroughly studied. The present study aimed to evaluate the frequency of KSHV genotypes isolated from KS tissues in Classical KS and AIDS KS patients from Xinjiang, China. ORF-K1 of KSHV from tissue samples of 28 KS patients was amplified and sequenced. Two subtypes of KSHV were identified according to K1 genotyping. Twenty-three of them belonged to subtype A, while five of them were subtype C. More genotype A than genotype C strains were found in both Classical KS and AIDS KS. No significant difference was found in the prevalence of different genotype between Classical KS and AIDS KS.

African Kaposi's sarcoma in the light of global AIDS: antiblackness and viral visibility.

Drawing on the theoretical frameworks of antiblackness and intersectionality and the concept of viral visibility, this essay attends to the considerable archive of research about endemic Kaposi's sarcoma (KS) in sub-Saharan Africa accrued during the mid-20th century. This body of data was inexplicably overlooked in Western research into KS during the first decade of the AIDS epidemic, during which period European and Mediterranean KS cases were most often cited as precedents despite the volume of African data available. This paper returns to the research on KS conducted in Africa during the colonial and postcolonial period to consider visibility, racial erasure, and discourses of global epidemiology, suggesting that the dynamics of medical research on HIV/AIDS have proceeded according to a tacit paradigm of antiblackness manifest in multiple exclusions of Africa from global health agendas--most recently the exclusion of the region from antiretroviral (ARV) drug therapy during the first decades of the treatment's availability. During that decade KS all but disappeared among people with access to ARV therapy while KS became even more prevalent in sub-Saharan Africa, escalating along with HIV.

Incidence of primary skin cancer after organ transplantation: An 18-year single-center experience in Korea.

BACKGROUND: Skin cancer is the most common malignancy to arise after organ transplantation in Caucasians, but limited data are available on its incidence in Asian transplant recipients. OBJECTIVE: We sought to assess the incidence of skin cancer after organ transplantation in a Korean cohort. METHODS: A cohort study was conducted to determine the incidence and risk factors for skin cancers among kidney, liver, heart, or pancreas transplant recipients, treated at the Asan Medical Center in Seoul, Korea. RESULTS: The cumulative incidences of skin cancer were 0.70% at 5 years, 1.66% at 10 years, and 2.31% at 15 years. For all skin cancers, squamous cell carcinoma, basal cell carcinoma, and Kaposi sarcoma, the standardized incidence ratios between the recipients and the Korean general population were 30.9 (95% confidence interval, 12.4-63.6), 61.9 (12.8-180.8), 11.9 (0.3-66.1), and 565.2 (68.4-2041.6) after the end of the fifth posttransplantation year, respectively. LIMITATIONS: We cannot exclude the possibility of both the underestimation because of potential missing cases and the overestimation because of the ascertainment bias. CONCLUSION: The incidence of posttransplantation skin cancer is very low in Korean patients. However, the risk of skin cancer in organ transplant recipients may be considerably higher than that in the Korean general population.

Familial classic Kaposi sarcoma in two siblings: case report and literature review.

BACKGROUND: Kaposi sarcoma (KS) is a cutaneous endothelial vascular proliferation with four subtypes: iatrogenic, acquired immune deficiency syndrome (AIDS) related, African, and classic. Familial cases of KS are rare, with 72 cases reported to date, and all were described with the classic variant. The occurrence of classic KS in the Jewish population is well documented, and most of the familial classic KS cases were also reported in Jewish families. OBJECTIVE: We briefly present the history, biopsies, laboratory data, diagnosis, and treatment of localized lower limb classic KS in two siblings of Jewish Eastern European ethnic descent with their response to different therapy modalities. One of our cases had the second longest reported period of follow-up for familial classic KS of 40 years.

Evaluation of c-kit expression in classic Kaposi's sarcoma in a cohort of Egyptian patients.

BACKGROUND: Kaposi's sarcoma (KS) is an angioproliferative disorder associated with human herpesvirus 8 infection. Classic KS is the most prevalent type of KS in countries of the Mediterranean basin including Egypt. Several in vitro studies have detected c-kit expression in AIDS related-KS however, only a few studies addressed this issue in the classic type with no data on the ethnicity of studied cases. The prospect of installing targeted anti- c-kit treatment to KS patients presents a promising avenue in KS therapeutics. AIM: To elucidate the expression of c-kit in classic KS cases and study possible relations with expression of HHV8 latency-associated nuclear antigen-1 (LANA-1) and other clinicopathological parameters. METHODS: Twenty four cases of classic KS of the plaque and nodular stages in the lower limb were studied. Immunohistochemical detection of HHV8-LANA-1 and c-kit was carried out on archival paraffin embedded tissue, possession of the Pathology and Dermatology Departments, Alexandria School Of Medicine, Egypt. Statistical analysis of possible relations between both antigens and clinicopathological parameters (patient's age and gender and histological stage) was performed. RESULTS: HHV8 expression was detected in 100% of cases while c-kit immunoreactivity was found in 54.2% of cases. There was no correlation between c-kit and HHV8 immunoreactivity or any of the studied clinicopathological parameters. CONCLUSIONS: This is the first report of c-kit expression in classic KS in an ethnically homogeneous cohort of Arabs of the Mediterranean region. We detected c-kit expression in about half the cases with no relationship to HHV8 LANA expression or clinicopathological parameters.

Seroprevalence and risk factors of Kaposi's sarcoma-associated herpesvirus infection among the general Uygur population from south and north region of Xinjiang, China.

BACKGROUND: Kaposi sarcoma (KS) is a complex multifocal neoplasm and is the major cause of death for about 50% of acquired immunodeficiency syndrome (AIDS) patients. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus with a causal role in the development of all types of KS. KS is prevalent among the Uygur people in Xinjiang, especially in south area. Here we carried out a cross-sectional study among 1534 general Uygur individuals from south and north region of Xinjiang to assess the seroprevalence of KSHV and to identify the potential correlation between KSHV seroprevalence and KS incidence. RESULTS: Seroprevalence of KSHV in South and North Xinjiang was 23.1% and 25.9%, respectively. Older age was independently associated with higher KSHV seroprevalence. In subjects from South Xinjiang, lower educational level and reported drinking were each independently associated with higher KSHV seroprevalence. Furthermore, the antibody titer was significantly lower in both south and north KSHV seropositive individuals compared with KS patients, as analyzed by gradient dilution (P < 0.001). CONCLUSION: KSHV is highly prevalent in the general Uygur population in both South and North Xinjiang. Interestingly, the infection rate of KSHV in these two geographical areas did not correlate well with KS incidence. Perhaps unknown factors exist that promote the progression of KSHV infection to KS development in the local minority groups.

Kaposi sarcoma presenting as yellow-green penile plaques in a black man with HIV.

Kaposi sarcoma characteristically presents with violaceous papules, plaques, or nodules due to the vascular nature of the lesions. We present the case of a human immunodeficiency virus (HIV)-positive black man with yellow-green penile plaques. Biopsy results revealed leukoedema and slitlike vascular spaces. Immunohistochemistry was positive for CD31 and CD34. He was treated with highly active antiretroviral therapy (HAART) and the penile plaques improved. Localized yellow-green penile plaques are an uncommon presentation of the well-known clinical entity, Kaposi sarcoma. This case underscores the varied clinical presentations that can occur in skin of color and the importance of histopathology in the assessment of uncharacteristic clinical presentations, especially in immunosuppressed patients.

Classic Kaposi's sarcoma in Arabs--widening ethnic involvement.

Kaposi's sarcoma is a tumor caused by human herpes virus 8 also known as Kaposi sarcoma-associated herpes virus. Originally described by Kaposi in 1872, this tumor is recognized as an AIDS-defining illness. Classic Kaposi's sarcoma (CKS) is a relatively indolent disease affecting elderly men from the Mediterranean region or of eastern European descent, besides Jews in whom it is the most common. It has been also reported in the Arab population living in Israel. Kaposi's sarcoma has been reported in Arabs after kidney transplantation; however, there are no reports of CKS occurring in non-Israeli Arabs. This is first such article reporting two Arab patients who presented with CKS thus widening the ethnic and geographic area of involvement with this condition.

Trends in Kaposi's sarcoma survival disparities in the United States: 1980 through 2004.

BACKGROUND: Kaposi's sarcoma (KS) is the most common cancer diagnosed among people with HIV in the United States. Highly active antiretroviral therapy (HAART) is an essential treatment for KS, and recent reports document the emergence of racial disparities in KS incidence and HIV-related mortality in the post-HAART era (1996 to present). The aim of this study was to examine trends in KS survival by race from the beginning of the HIV epidemic through the introduction of HAART. METHODS: Median cause-specific survival and adjusted hazard ratios for KS from 1980 to 2004 were calculated by race using Surveillance, Epidemiology, and End Results nine-area data. RESULTS: Median survival among both black and white patients was relatively constant until 1995 (average median survival, 14 and 18 months, respectively). In 1996, white patients experienced an increase in median survival to 103 months. In subsequent years, the increase in median survival was so great that white patients did not reach 50% mortality (follow-up ending December 31, 2007). Survival among black patients increased gradually until its peak in 2001 when median survival had not been reached after 83 months of follow-up. However, subsequent relative decreases to 35 months occurred in 2002 and 2004. CONCLUSIONS: The current analysis provides evidence that there have been substantial increases in KS survival among white patients in the HAART era. Black patients have also experienced some improvements but to an attenuated extent. IMPACT: Careful attention should be paid to the continuing evolution of trends in KS survival and survival disparities.

Classic Kaposi's sarcoma in Han Chinese and useful tools for differential diagnosis.

Kaposi's sarcoma (KS) is a common AIDS-related malignant neoplasm in the head and neck region, especially in the oral cavity, but is rarely described in the HIV-negative and non-immunosuppressed individual. Our case is of interest, because it is the first case in which manifestation of the KS occurred in the face and head areas in a patient with a Han ethnic background who had an adequate immune system. The lesions were diagnosed as angiosarcomas twice. The clinical presentation, therapeutic options, and tools for differentiating Kaposi sarcoma from other vascular and nonvascular spindle cell lesions are presented, and the relevant literature is reviewed.

TP53 codon 72 polymorphism in classic, endemic and epidemic Kaposi's sarcoma in African and Caucasian patients.

OBJECTIVES: Several studies have examined the association of codon 72 polymorphism of the TP53 gene, encoding either arginine or proline, in several tumor types but none have investigated its role in Kaposi's sarcoma (KS) development. METHODS: In this prevalent case-control study, 67 cutaneous lesions of classic, iatrogenic, endemic as well as epidemic KS from African (n = 22) and Caucasian (n = 45) patients, and blood samples from 150 healthy controls (n = 57 African, n = 93 Caucasian) have been analyzed for arginine and proline allele distribution. RESULTS: Among African cases the proline homozygous, heterozygous and arginine homozygous genotype frequencies were 50.0, 31.8 and 18.2%, respectively, and among controls 54.4, 40.3, and 5.3%, respectively (p = 0.1872). Conversely, among Caucasian cases genotype distributions were 6.7, 55.6, and 37.8%, and among controls 7.5, 34.4, and 58.1%, respectively (p = 0.0567). No significant differences in arginine and proline allele distribution were observed when the cases were stratified by HIV status/tumor type. CONCLUSIONS: The results obtained in this study suggest that p53 polymorphism at codon 72 does not represent a risk factor for the development of all forms of KS, either among African or among Caucasian populations.