HIV-associated Kaposi's Sarcoma Research Articles

Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings.

Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment. Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study

IntroductionThe expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria.MethodsWe analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria’s largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006–2009 as the pre-expansion period and 2010–2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders.ResultsAmong 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01–2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010–2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010–2016 compared to 2006–2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006–2009 and 2010–2016 after adjusting for age, sex, and CD4 T-cell count.ConclusionThe expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

Generalized HIV-associated kaposi's sarcoma with multiorgan lesion in a comorbid patient

Generalized HIV-associated kaposi's sarcoma with multiorgan lesion in a comorbid patient

BI12 The incidence and survival of Kaposi sarcoma using national cancer registry data

Abstract Kaposi sarcoma (KS) is a rare soft tissue endothelial neoplasm associated with human herpesvirus (HHV)-8 infection. Four types of KS are recognized, with the majority of cases in the West attributed to HIV-associated KS or, less frequently, to iatrogenic KS caused by systemic immunosuppression. Population-based data on KS epidemiology in England are lacking, with the last published evaluation dating back to the 1980s. More recently, data on KS epidemiology have been included in the National Cancer Registration and Analysis Service’s (NCRAS) ‘Get Data Out’ annual reports, with details published from 2013 to 2019. A nonsignificant reduction in the incidence rate of KS in England was observed from 2013 [0.271; 95% confidence interval (CI) 0.229–0.319] to 2019 (0.222, 95% CI 0.185–0.265; www.cancerdata.nhs.uk/getdataout/kaposi_sarcoma). This figure is slightly lower than the most recent reported crude incidence rates of KS in Europe from 2000 to 2007 (0.28) and significantly lower than that of the USA in 2017 (0.45) and globally in 2020 (0.439) (https://gco.iarc.fr/today/data/factsheets/cancers/19-Kaposi-sarcoma-fact-sheet.pdf). Data from NCRAS show that most cases of KS in England were diagnosed following a general practitioner referral (32.8%), outside the 2-week wait route (15.6%). A noteworthy proportion of cases (17.2%) were diagnosed following an emergency presentation to the emergency department, emergency clinician referrals or acute admissions. The 5-year net survival after the diagnosis of KS was stable at 81.3% (95% CI 73–89.5), 86.8% (95% CI 79.5–94.1) and 79.7% (95% CI 67.2–92.2) for 2013, 2014 and 2015, respectively (www.cancerdata.nhs.uk/getdataout/kaposi_sarcoma). These data provide a useful insight into the epidemiology of this rare cancer; however, it is probable that the true incidence of KS is under-reported, particularly in cases where there is no histological confirmation or reporting of KS on the death certificate, which may be more likely in patients who were HIV positive. Lack of knowledge of the underlying cause for KS is a major limitation. In conclusion, there is a paucity of published data on KS epidemiology in England. Further evaluation of KS subsets, patient demographics and comorbidity at diagnosis is needed to allow a better understanding of differences in the KS incidence in England in comparison with global figures.

Upregulation of Cell Surface Glycoproteins in Correlation with KSHV LANA in the Kaposi Sarcoma Tumor Microenvironment.

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein was evaluated for its expression and co-localization with KSHV LANA using multi-color immunofluorescence in KS tissues, KSHV-infected L1T2 cells, uninfected TIVE cells, and murine L1T2 tumor xenografts. Five surface glycoproteins (KDR, FLT4, UNC5A, ADAM12, and CD34) were associated with LANA-positive cells but were also detected in uninfected cells in the KS microenvironment. In vitro L1T2 cultures showed evidence of only FLT4, KDR, and UNC5A, whereas mouse L1T2 xenografts recapitulated human KS cell surface expression profiles, with the exception of CD34 and Prox-1. In KS tumors, most LANA-positive cells co-expressed markers of vascular as well as lymphatic endothelial lineages, suggesting KS-associated dedifferentiation to a more mesenchymal/progenitor phenotype.

114TiP Preliminary assessment of safety and tolerability of dostarlimab in combination antiretroviral therapy (cART)-refractory HIV-associated Kaposi sarcoma (StarKap)

114TiP Preliminary assessment of safety and tolerability of dostarlimab in combination antiretroviral therapy (cART)-refractory HIV-associated Kaposi sarcoma (StarKap)

A prospective study of clinical outcomes of HIV-associated and HIV-negative Kaposi sarcoma in Uganda.

Improved understanding of the effect of HIV infection on Kaposi sarcoma (KS) presentation and outcomes will guide development of more effective KS staging and therapeutic approaches. We enrolled a prospective cohort of epidemic (HIV-positive; HIV + KS) and endemic (HIV-negative; HIV - KS) KS patients in Uganda to identify factors associated with survival and response. Adults with newly diagnosed KS presenting for care at the Uganda Cancer Institute (UCI) in Kampala, Uganda, between October 2012 and December 2019 were evaluated. Participants received chemotherapy per standard guidelines and were followed over 1 year to assess overall survival (OS) and treatment response. Two hundred participants were enrolled; 166 (83%) had HIV + KS, and 176 (88%) were poor-risk tumor (T1) stage. One-year OS was 64% (95% confidence interval [CI] 57-71%), with the hazard of death nearly threefold higher for HIV + KS (hazard ratio [HR] = 2.93; P = 0.023). Among HIV + KS, abnormal chest X-ray (HR = 2.81; P = 0.007), lower CD4 + T-cell count (HR = 0.68 per 100 cells/μl; P = 0.027), higher HIV viral load (HR = 2.22 per log 10 copies/ml; P = 0.026), and higher plasma Kaposi sarcoma-associated herpesvirus (KSHV) copy number (HR = 1.79 per log 10 copies/ml; P = 0.028) were associated with increased mortality. Among HIV - KS, factors associated with mortality included Karnofsky score <70 (HR = 9.17; P = 0.045), abnormal chest X-ray (HR = 8.41; P = 0.025), and higher plasma KSHV copy number (HR = 6.21 per log 10 copies/ml; P < 0.001). Although survival rates were better for HIV - KS than HIV + KS, the high mortality rate seen in both groups underscores the urgent need to identify new staging and therapeutic approaches. Factors associated with mortality, including high plasma KSHV, may serve as important targets of therapy.

Understanding Diagnostic Delays for Kaposi Sarcoma in Kenya: A Qualitative Study.

Although HIV-associated Kaposi sarcoma (KS) is frequently diagnosed at an advanced stage in sub-Saharan Africa, reasons for diagnostic delays have not been well described. We enrolled patients >18 years with newly diagnosed KS between 2016 and 2019 into the parent study, based in western Kenya. We then purposively selected 30 participants with diversity of disease severity and geographic locations to participate in semistructured interviews. We used 2 behavioral models in developing the codebook for this analysis: situated Information, Motivation, and Behavior framework and Andersen model of total patient delay. We then analyzed the interviews using framework analysis. The most common patient factors that delayed diagnosis were lack of KS awareness, seeking traditional treatments, lack of personal efficacy, lack of social support, and fear of cancer, skin biopsy, amputation, and HIV diagnosis. Health system factors that delayed diagnosis included previous negative health care interactions, incorrect diagnoses, lack of physical examination, delayed referral, and lack of tissue biopsy availability. Financial constraints were prominent barriers for patients to access and receive care. Facilitators for diagnosis included being part of an HIV care network, living near health facilities, trust in the health care system, desire to treat painful or disfiguring lesions, and social support. Lack of KS awareness among patients and providers, stigma surrounding diagnoses, and health system referral delays were barriers in reaching KS diagnosis. Improved public health campaigns, increased availability of biopsy and pathology facilities, and health provider training about KS are needed to improve early diagnosis of KS.

SARS-CoV-2-Specific T Cell Immunity in HIV-Associated Kaposi Sarcoma Patients in Zambia.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus is the cause of coronavirus disease 2019 (COVID-19). It has caused millions of infections and deaths globally over a 2-year period. Some populations including those living with HIV and/or cancer are reported to be at a higher risk of infection and severe disease. HIV infection leads to a depletion of CD4+ T cells which impairs cell-mediated immunity and increases the risk of malignancies such as Kaposi sarcoma (KS) and viral infections such as SARS-CoV-2. However, several other factors including level of immunosuppression and chemotherapy may also affect the immune response against SARS-CoV-2. In this study, we investigated factors affecting SARS-CoV-2-specific T cell immunity towards the spike, nucleoprotein, membrane protein, and other open reading frame proteins in individuals with HIV-associated KS. The KS patients were SARS-CoV-2 seropositive with detectable T cell responses, but had no history of symptomatic SARS-CoV-2 infection. We observed that the T cell responses increase from baseline levels during follow-up, with responses towards the NMO peptide pool being statistically significant. Low CD4 counts below 200 cells/μl were associated with lower SARS-CoV-2-specific T cell responses. Cancer chemotherapy and KS T staging did not have a significant effect on the T cell responses.

Telling the story of intersectional stigma in HIV-associated Kaposi's sarcoma in western Kenya: a convergent mixed-methods approach.

IntroductionThe experience of stigma can be multifaceted for people with HIV and cancer. Kaposi's sarcoma (KS), one of the most common HIV‐associated cancers in sub‐Saharan Africa, often presents with visible skin lesions that may put people at risk for stigmatization. In this way, HIV‐associated KS is unique, as people with KS can experience stigma associated with HIV, cancer, and skin disease simultaneously. The aim of this study is to characterize the intersectionality of HIV‐related, cancer‐related and skin disease‐related stigma in people living with HIV and KS.MethodsWe used a convergent mixed‐methods approach nested within a longitudinal study of people with HIV‐associated KS in western Kenya. Between February 2019 and December 2020, we collected quantitative surveys among all participants and conducted semi‐structured interviews among a purposive sample of participants. Quantitative surveys were adapted from the abridged Berger HIV Stigma Scale to assess overall stigma, HIV‐related stigma, cancer‐related stigma, and skin disease‐related stigma. Qualitative data were coded using stigma constructs from the Health Stigma and Discrimination Framework.ResultsIn 88 semi‐structured interviews, stigma was a major barrier to KS diagnosis and treatment among people with HIV‐associated KS. Participant's stories of stigma were dominated by HIV‐related stigma, more than cancer‐related or skin disease‐related stigma. However, quantitative stigma scores among the 117 participants were similar for HIV‐related (Median: 28.00; IQR: 28.0, 34.0), cancer‐related (Median: 28.0; IQR: 28.0, 34.8), and skin disease‐related stigma (Median: 28.0; IQR: 27.0, 34.0). In semi‐structured interviews, cancer‐related and skin disease‐related stigma were more subtle contributors; cancer‐related stigma was linked to fatalism and skin‐related stigma was linked to visible disease. Participants reported resolution of skin lesions contributed to lessening stigma over time; there was a significant decline in quantitative scores of overall stigma in time since KS diagnosis (adjusted β = –0.15, p <0.001).ConclusionsThis study highlights the role mixed‐method approaches can play in better understanding stigma in people living with both HIV and cancer. While HIV‐related stigma may dominate perceptions of stigma among people with KS in Kenya, intersectional experiences of stigma may be subtle, and quantitative evaluation alone may be insufficient to understand intersectional stigma in certain contexts.

S1 Guidelines for the Kaposi Sarcoma.

Kaposi's sarcoma (KS) is a rare, malignant, multilocular vascular disease originating from lymphatic endothelial cells that can primarily affect the skin and mucous membranes, but also the lymphatic system and internal organs such as the gastrointestinal tract, lungs or liver. Five epidemiological subtypes of KS with variable clinical course and prognosis are distinguished, with increased incidence in specific populations: (1) Classical KS, (2) Iatrogenic KS in immunosuppression, (3) Endemic (African) lymphadenopathic KS, (4) Epidemic, HIV-associated KS and KS associated with immune reconstitution inflammatory syndrome (IRIS), and (5) KS in men who have sex with men (MSM) without HIV infection. This interdisciplinary guideline summarizes current practice-relevant recommendations on diangostics and therapy of the different forms of KS. The recommendations mentioned in this short guideline are elaborated in more detail in the extended version of the guideline (online format of the JDDG).

Characteristics and Treatment Response of Patients with HIV Associated Kaposi's Sarcoma in Central Kenya.

Kaposi's sarcoma (KS) is the most common HIV-associated malignancy in Sub Saharan Africa. In 2018, it was the 7th most common cancer and the 10th most common cause of cancer death in Kenya. This study aimed to describe the baseline and clinical characteristics and treatment response observed following combined antiretroviral treatment (ART) and chemotherapy in KS patients. This was a descriptive analysis of patients aged ≥15 years treated for KS and HIV at 11 treatment hubs in Central Kenya between 2011 and 2014. Data on baseline and clinical characteristics, ART and chemotherapy regimens as well as treatment responses were collected from patient files and KS registers. A total of 95 patients presenting with clinically suspected KS with no history of prior treatment with chemotherapy were reviewed. All had histological diagnostic samples taken with 67 (71%) having confirmed KS. All were on ART, either newly initiated or continuing on ART, and 63 of the 67 (94.0%) confirmed to have KS received chemotherapy. Among the 67 patients with confirmed KS, mean age was 37.2 years (± 13.2) and 40 (59.7%) were male. More than 80% had normal baseline and follow-up BMI, and 34 (50.7%) were on a TDF-based regimen, 52 (77.6%) were treated with the Adriamycin, bleomycin and vinblastine protocol, and 55 (82.1%) had KS diagnosis before HIV diagnosis. All 67 patients had mucocutaneous lesions. Complete, partial response and stable disease occurred in 27 (40.3%), 10 (14.9%) and 7 (10.4%), respectively, 11 (16.4%) defaulted care during treatment, six patients died during treatment, four patients died before treatment while two patients had progressive disease during chemotherapy. The diagnosis of KS preceded HIV in the majority of cases reviewed, with histology helpful to reduce misdiagnosis. Patients generally complied with their chemotherapy, with overall good response rate for this intervention implemented at primary health-care facilities.

Effectiveness and Safety of Treatment with Neodymium:YAG Laser 1064 nm in Patients with Classic and Epidemic Kaposi Sarcoma.

Kaposi’s sarcoma (KS) is a vascular neoplasm Herpes Virus 8 (HHV8), which can affect the skin, mucous membranes and viscera. There is currently no standard treatment for KS; this study evaluated the efficacy and safety of Neodymium:YAG (Nd:YAG) laser 1064 nm treatment in patients with classic and HIV-associated KS. 15 patients with classic KS (group A) and 15 with epidemic KS (group B), with exclusively cutaneous localization, were treated with Nd:YAG laser 1064 nm. Four treatment sessions were performed at 4 weeks intervals. 24/30 (80%) of treated patients underwent clinical improvement. Better results have been obtained in HIV-positive patients, especially in terms of reduced lesion size and the flattening of elevated lesions. The 1064 nm Nd:YAG laser is effective and safe in the treatment of classic and epidemic KS, especially in patients with symptomatic, slow-progressing local disease, where other treatment options may be inappropriate.

Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial.

PURPOSEEvaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema.METHODSA randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted.RESULTSOf 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was –25.9 (34.6) for the control arm compared with –13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was –12.6 (–39.3 to 14.1).CONCLUSIONFuture studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.

Disseminated HIV-associated Kaposi sarcoma with lung involvement: a clinical case

<h3></h3> Немаловажную роль в ряду различных клинических проявлений ВИЧ-инфекции играет патология кожи и слизистых оболочек. В условиях нарастающей иммуносупрессии при ВИЧ-инфекции многие заболевания кожи и слизистых оболочек имеют тенденцию к более тяжелому течению, генерализации и сопровождаются поражением висцеральных органов, приводя к гибели больных. Авторы демонстрируют клинический случай генерализованной саркомы Капоши (СК) с поражением внутренних органов (легких) у больного с ВИЧ-инфекцией. Как правило, у пациентов с ВИЧ-положительным статусом развитие СК происходит при наличии выраженного иммунодефицита (CD4-лимфоциты &lt;200 кл/мкл), однако для данного пациента это не было характерным (CD4-лимфоциты &gt;360 кл/мкл), что соответствовало умеренному иммунодефицитному состоянию. Несмотря на проводимую этиопатогенетическую и симптоматическую терапию, у больного наблюдалась отрицательная клиническая динамика течения основного заболевания с нарастанием дыхательной и кардиоваскулярной недостаточности и через 20 дней была констатирована биологическая смерть. При проведении патологоанатомического и гистологического исследований описана морфология множественных очагов СК в легких. При этом клинический случай свидетельствует об отсутствии корреляции между кожными и висцеральными проявлениями СК. Дифференциальный диагноз проводился между полисегментарной пневмонией, туберкулезом легких и генерализованной формой СК. Авторы обсуждают возможные причины развития генерализованной СК при ВИЧ-инфекции у молодого пациента. К предикторам летального исхода у пациента следует отнести мультиморбидность, фульминантное развитие СК легких, анемию, тромбоцитопению, лейкоцитоз, гемоделюцию. Кроме того, возможно предположить формирование воспалительного синдрома восстановления иммунитета на фоне инициированной интенсивной поликомпонентной антиретровирусной терапии. Представленный клинический пример свидетельствует о возможном поражении СК легочной ткани при наличии не столь выраженных проявлений СК на коже и слизистых оболочках полости рта. Легочная форма СК в клинике встречается редко, но зачастую приводит к смерти.

Mortality disparities among patients with HIV-associated Kaposi's sarcoma in the southern United States.

To describe risk factors for mortality in HIV-associated Kaposi's sarcoma in an urban population in Dallas, Texas. Retrospective electronic medical record review of patients with HIV-associated Kaposi's sarcoma. Electronic medical records were reviewed from 1 January 2009 to 31 December 2018 for patients with a diagnosis of HIV and Kaposi's sarcoma by ICD-9 or ICD-10 codes. Demographics, HIV history, Kaposi's sarcoma history, treatment, and mortality data were collected. Mortality data was supplemented by an inquiry from the National Death Index (NDI). Survival analyses were performed using Cox proportional hazards analysis to determine independent predictors of mortality. Black patients had higher mortality than white or Hispanic patients (hazard ratio 2.07, 95% confidence interval 1.12-3.82), even after adjusting for covariates. This mortality difference correlates with higher rates of advanced Kaposi's sarcoma disease and KS-IRIS in black patients compared with other groups and is not explained by differences in CD4+ cell count, HIV viral load, engagement in care, or ART adherence at the time of cancer diagnosis. Despite nationwide trends showing decreased incidence and decreased mortality in Kaposi's sarcoma in the ART era, a high number of Kaposi's sarcoma cases and disparities in Kaposi's sarcoma outcomes persist in certain populations in the United States.

Oncologic Treatment of HIV-Associated Kaposi Sarcoma 40 Years on.

The observation in 1981 of the emergence of Kaposi sarcoma (KS) among young men who had sex with men was one of the first harbingers of the HIV epidemic. With advances in HIV care, the incidence of HIV-associated KS (HIV+KS) has decreased over time in the United States. However, it remains a persistent malignancy among some HIV-infected populations and is one of the most common tumors in sub-Saharan Africa. Because of the relapsing and remitting nature of this cancer, patients with HIV+KS can experience significant, long-term, morbidity. Patients with severe HIV+KS may also have concurrent lymphoproliferative syndromes, malignancies, and/or infections that can contribute to mortality. Several chemotherapy agents were explored in clinical trials for HIV+KS during the early stage of the epidemic. As HIV+KS emerges with CD4 lymphopenia and immunodysregulation, T-cell-sparing options are important to consider. Here, we explore the pathogenesis of HIV+KS and the current evidence for immunotherapy and therapies that potentially target KS pathogenesis. This review provides the current landscape of therapies for HIV+KS and highlights management issues for patients with HIV and cancer.

Pulmonary Kaposi's sarcoma—an atypical clinical presentation

HIV-associated Kaposi's sarcoma is an angioproliferative neoplasia caused by infection with human herpesvirus 8. It typically presents with mucocutaneous involvement. Pulmonary Kaposi's sarcoma is rare, and an uncommon form of initial presentation of the disease. The authors present the clinical case of an HIV-positive patient with Kaposi's sarcoma who had exclusively pulmonary involvement at diagnosis. This case is highlighted for its rarity, by the diagnostic challenge it presented, and for the important role of bronchoscopy as a diagnostic tool for this pathology. Bronchoscopy allows direct visualization of the lesions and the ability to perform a bronchoalveolar lavage and directed biopsies.

Viral and immunological markers of HIV-associated Kaposi sarcoma recurrence.

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy highly prevalent in Sub-Saharan Africa. The main objective of this study was to determine the factors associated with recurrence of HIV-associated KS. We recruited a cohort of individuals on antiretroviral therapy who were in remission for HIV-associated KS after undergoing cytotoxic cancer chemotherapy. Collected variables included sociodemographic and clinical parameters, cytokines and chemokines, HIV viral loads, and CD4 counts. Compared to individuals who had KS recurrence, IL-5 was significantly higher at time of follow-up in individuals who had sustained remission (22.7pg/ml vs. 2.4pg/ml; p = 0.02); IL-6 was significantly higher at baseline and time of follow-up in individuals who had sustained remission, (18.4pg/ml vs. 0pg/ml; p = 0.01) and (18.0pg/ml vs. 0.18pg/ml; p = 0.03) respectively; IP-10 was significantly lower at baseline and at time of follow-up in individuals who had sustained remission, (534pg/ml vs. 920pg/ml; p = 0.04) and (446pg/ml vs.1098pg/ml; p = 0.01) respectively; while HIV viral load was significantly lower at baseline and at time of follow-up in individuals who had sustained remission, (0copies/ml vs. 113copies/ml; p = 0.004) and (0copies/ml vs. 152copies/ml; p = 0.025) respectively. Plasma levels of IL-5, IL-6, and IP-10 are associated with recurrence of HIV-associated KS, while persistently detectable HIV viral loads increase the risk of KS recurrence.

Malignant Cutaneous Tumors

This chapter reviews the most common malignant cutaneous tumors. The section on malignant tumors of the epidermis discusses nonmelanoma skin cancer (i.e., basal cell carcinoma and squamous cell carcinoma) and malignant melanoma. The section on malignant tumors of the dermis covers metastatic tumors, primary tumors (Merkel cell carcinoma, Paget disease, extramammary Paget disease, angiosarcoma, and dermatofibrosarcoma protuberans), and Kaposi sarcoma (i.e., classic Kaposi sarcoma, African Kaposi sarcoma, organ-transplant Kaposi sarcoma, and HIV-associated Kaposi sarcoma). The final section covers cutaneous lymphomas. The coverage of each disease includes a discussion of epidemiology, etiology, diagnosis, differential diagnosis, treatment, and prognosis. Tables provide the adjusted estimated relative risks of melanoma by nevus type and number, the American Joint Committee on Cancer (AJCC) TNM classification and staging system, the estimated probability of 10-year survival in patients with primary cutaneous melanoma, and an overview of overview of therapy for cutaneous T cell lymphoma. Figures illustrate the presentation of many malignant cutaneous tumors. This review contains 10 highly rendered figures, 5 tables, and 105 references.