Kaposi's Sarcoma Research Articles

BackgroundKaposi sarcoma (KS) is an angioproliferative tumor caused by human herpesvirus 8 and is an AIDS-defining illness. Combination antiretroviral therapy (ART) was introduced in the United States in 1996, after which U.S. KS incidence declined and survival improved; however, persistent racial and sex disparities remain. Our aim was to characterize 1999–2020 trends in KS incidence and mortality in the United States overall, and by race and sex, and to quantify changes in disparities over time.MethodsWe extracted KS case and death counts from the CDC WONDER database (ICD-10 codes B21.0, C46). Age-adjusted incidence rates (AAIR) and mortality rates (AAMR) per 100,000 were calculated by year, race, and sex. Temporal trends were evaluated using the Mann–Kendall test (Kendall’s τ), and between-group differences by t-test (α = 0.05).ResultsFrom 1999 to 2020, 27,886 KS cases and 4,380 deaths occurred. Overall AAIR was 0.99 in men versus 0.10 in women, and AAMR 0.16 versus 0.01 (both p < 0.001). Black men experienced the highest AAIR (2.23) and AAMR (0.40), significantly exceeding White men (0.79 and 0.13; p < 0.001). Incidence declined in both sexes (men: -46.7%, τ = -0.920; women: -58.9%, τ = -0.848; both p < 0.001). Mortality declined in men (-66.4%, τ = -0.581; p < 0.001). Among women, AAMR levels were very low throughout (mean ≈ 0.01 per 100,000); the end-to-end change from 1999 to 2020 was + 28.6%, yet the Mann–Kendall test did not identify a monotonic trend (τ = − 0.303; p = 0.060), reflecting early declines followed by year-to-year fluctuation around a low baseline.ConclusionAlthough KS incidence and mortality have declined markedly since 1999, Black men remain disproportionately affected. Focused public health efforts and enhanced access to HIV care are essential to close these gaps.Clinical trial numberNot applicable.

Kaposi's sarcoma (KS) is a multicentric, polyclonal malignancy linked to Kaposi's sarcoma-associated herpesvirus (KSHV) infection. While significant advances have been made in understanding KSHV virology and the clinical characteristics of KS, the precise mechanisms of pathogenesis and cellular origins remain elusive. This review integrates clinical observations with the latest cutting-edge research to explore the nature and potential cellular precursors of KS. Multiple cell types have been proposed as potential KS oncogenic progenitors, including endothelial cells, mesenchymal stem cells (MSCs), and circulating endothelial progenitor cells (EPCs). KS progenitor cells are thought to be recruited to sites of inflammatory angio-hyperplasia, where they may undergo KSHV-mediated transformation. Intriguingly, KSHV has been shown to modulate both endothelial-to-mesenchymal transition (EndMT) and mesenchymal-to-endothelial transition (MEndT). By elucidating the mechanisms underlying KSHV-mediated cellular plasticity and the synergistic effects of inflammatory angio-hyperplasia and viral lytic reactivation in driving malignant transformation, we aim to deepen our understanding of KSHV-driven oncogenesis. This review highlights promising avenues for future research, including the potential role of KSHV in other mesenchymal-derived sarcomas, such as osteosarcoma. Ultimately, unraveling the complex interactions between KSHV, host cells, and the tumor microenvironment may pave the way for novel therapeutic strategies for patients with KS and related malignancies.

Immune profiling in solid organ transplant recipients with HHV-8 infection: Identification of immunological biomarkers for KICS and Kaposi's sarcoma.

Kaposi sarcoma: today, yesterday, and tomorrow.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and several lymphoproliferative diseases. As with all herpesviruses, KSHV replicates in a biphasic manner, with the establishment of a latent, persistent infection from which reactivation occurs, resulting in the completion of the temporal lytic replication cycle and production of infectious virions. Herein, we discuss the impact of KSHV lytic replication on the host cell nucleus and nuclear-related pathways. We highlight the dramatic remodelling of the nuclear architecture driven by the formation of viral replication and transcription centres (vRTCs), and the implications for sub-nuclear organelles, and how pathways involved in DNA damage, ribosomal biogenesis and epitranscriptomic regulation are disrupted or modified during KSHV replication. These changes foster an environment favourable for KSHV replication and may provide novel targets and strategies for therapeutic intervention.

ABSTRACT Kaposi sarcoma (KS) is a vascular neoplasm associated with human herpesvirus 8 (HHV‐8), typically affecting immunocompromised individuals. However, emerging reports describe cases in HIV‐negative men who have sex with men (MSM), constituting a proposed non‐epidemic variant. We report the case of a 50‐year‐old immunocompetent MSM who presented with violaceous papules on the right foot, histologically confirmed as KS. Extensive workup ruled out systemic involvement and HIV infection. Initial treatment with CO₂ laser achieved partial response, but lesion recurrence prompted additional laser interventions, including pulsed dye laser (PDL), 532‐nm KTP laser and combined PDL/Nd:YAG laser therapy. Despite multiple sessions and varied parameters, no significant clinical improvement was observed, and disease progression continued with new lesions affecting contralateral and distant sites. Ultimately, radiotherapy was administered, achieving complete remission. This case illustrates the diagnostic and therapeutic challenges of non‐epidemic KS. Although laser therapies are increasingly used for localized KS, especially for cosmetic and symptomatic relief, their efficacy remains variable. Our findings align with prior reports demonstrating inconsistent outcomes and high recurrence rates following laser monotherapy. This case underscores the necessity of individualized treatment planning and highlights radiotherapy as an effective option for refractory disease. Furthermore, it emphasizes the need for heightened clinical awareness of KS in HIV‐negative MSM, even in the absence of immunosuppression. Continued investigation is warranted to define optimal treatment strategies for this KS variant and to clarify the role of laser modalities in long‐term disease control.

Vascular anomalies (VAs) require specialized multidisciplinary management. Bleomycin electrosclerotherapy (B)EST combines electroporation with intralesional bleomycin to enhance drug uptake while preserving surrounding tissue. Its role in treating VAs remains largely unexplored. This systematic review evaluates the efficacy, safety, and procedural protocols of BEST in VA treatment. Following PRISMA guidelines, a systematic search was conducted in PubMed, Web of Science, and Scopus. Inclusion criteria included peer-reviewed studies on (B)EST for VAs, excluding reviews, editorials, and animal studies. Among 1237 records, 15 studies met the inclusion criteria, published between 2012 and 2025, primarily from Europe (13/15). A total of 566 patients were treated, including 445 with vascular malformations and 121 with vascular tumors (Kaposi sarcoma, angiosarcoma). (B)EST was mainly applied to slow-flow malformations. Across VA types, lesion-volume or symptom reduction rate was high, with five studies each reporting a 100% rate. Complete response in vascular tumors ranged from 65 to 100%. Most studies followed current guidelines, with bleomycin doses between 200 and 10,000 IU per session. Adverse effects were primarily local and self-limiting (Cardiovascular and Interventional Radiological Society of Europe classification CIRSE 1a-2); ulcerations occurred mainly in vascular tumors (CIRSE 3a); and skin hyperpigmentation (CIRSE 1a) was observed frequently, often partially resolving over time. BEST shows promise for VA treatment, particularly venous and lymphatic malformations. While results suggest efficacy and safety, treatment heterogeneity and long-term outcomes require further investigation. Optimizing tailored protocols for each VA subtype and presentation is essential for defining (B)EST's role in VA management. Question What is the role and efficacy of (bleomycin) electrosclerotherapy (B)EST in managing vascular anomalies resistant to conventional treatments, including tumors and malformations? Findings (B)EST demonstrated significant efficacy, achieving 65-100% complete responses in vascular tumors and 54.9-100% lesion or symptom reduction in vascular malformations. Clinical relevance (B)EST offers an option for patients with treatment-resistant or recurrent vascular anomalies, improving symptom-related outcomes. This is tempered by the absence of controlled trials, the need for cumulative dose pulmonary monitoring and the potential cosmetic burden of hyperpigmentation.

Interactions between viral glycoproteins and cellular receptors determine virus tropism and represent promising targets for vaccines. Eph receptor tyrosine kinases are conserved receptors for the human oncogenic gammaherpesviruses, Kaposi sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), and mediate entry into target cells by interaction with the viral gH/gL glycoprotein complex. To evaluate the use of murine gammaherpesvirus 68 (MHV68), a natural pathogen of rodents, as an in vivo model system for early events in gammaherpesvirus infection, we characterized the interaction of the MHV68 gH/gL complex with Eph receptors. We demonstrate a direct interaction of MHV68 gH/gL with EphA4 and EphB3, that is conserved between human and murine receptors. Pre-incubation of MHV68 inocula with soluble decoy receptors decreased infection of permissive fibroblasts. Ectopic expression of EphA4 and EphB3 enabled MHV68 to infect otherwise non-permissive human B cells, demonstrating EphA4 and EphB3 receptor function. Targeted mutations informed by protein structure predictions demonstrate that the MHV68 gH/gL-Eph interaction is determined by domain I (D-I) and follows structural motifs previously described in the KSHV gH/gL-EphA2 complex. The importance of gH D-I is further highlighted by the analysis of gH-targeting neutralizing antibodies. Antibody adsorption via the full gH ectodomain or gH D-I led to comparable reductions in neutralization capacity of serum from WT infected mice, indicating the Eph-binding domain is a major target for gH/gL-directed neutralizing antibodies. Our study characterizes Eph receptors as novel interaction partners and entry receptors for MHV68. Conservation of entry mechanisms provides the basis for future in vivo analyses of the contribution of Eph receptors to cell-type dependent MHV68 infection, as well as targeted strategies to prevent transmission and diseases associated with chronic infection.

Kaposi’s sarcoma (KS) is a tumor that primarily affects the skin, caused by a multifactorial pathogenesis mediated through immune dysfunction, often leading to increased morbidity and mortality in Sub-Saharan Africa (SSA). Human herpesvirus-8, also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), induces an infection that can facilitate the pathogenesis of KS and other conditions. All KSHV subtypes depend on the expression of specific markers, such as K1 proteins, which play critical roles in their life cycles. The infection is unevenly scattered worldwide, with individuals infected with human immunodeficiency virus (HIV) and pregnant women being among the most vulnerable groups. HIV infection and related effectors, such as TAT proteins, have substantial impacts on KSHV infectiousness, angiogenesis, various signaling pathways, and KS pathogenesis. Africa endures the heaviest burden of KS, which affects both men and women, sometimes from an early age. KS’s pathogenesis and underlying mechanisms remain unclear; this study aims to highlight the dynamics to be considered in managing and mitigating the burden of KS in SSA. In that region, certain infections are endemic and can cause intermediate health damage leading to KS tumorigenesis, highlighting the link between non-communicable and communicable diseases.

The strategies adopted by viruses to counteract the potential antiviral effects of ribosomal quality control (RQC) that regulates the fidelity of protein translation, ribosome recycling, and the activation of ribosomal and integrated stress responses are poorly understood. Here, we investigated the capacity of the viral ubiquitin deconjugase (vDUB) encoded in the large tegument protein of human pathogenic herpesviruses to interfere with the triggering of RQC upon the induction of translational stress in cytosolic and endoplasmic reticulum (ER)-associated ribosomes. We found that the vDUBs encoded by Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and Kaposi sarcoma virus (KSHV) share the capacity to counteract the ubiquitination of RPS10, RPS20, and RPS3, and the UFMylation of RPL26 in cells treated with the translation elongation inhibitor anisomycin (ANS), which resulted in the rescue of model RQC and ER-RQC substrates from proteasome- and lysosome-dependent degradation, readthrough of stall-inducing mRNAs, and inhibition of ER-phagy. In contrast, while inhibiting the ubiquitination of RPS10, RPS20, and RPS3, and rescuing RQC substrates almost as efficiently as the homologs, the herpes simplex virus-1 (HSV1) encoded vDUB failed to counteract RPL26 UFMylation. Furthermore, it was unable to rescue the ER-RQC substrate or inhibit ER-phagy, nor did it promote ZAKα phosphorylation or activate the ISR. Our findings pinpoint important differences in the strategies adopted by these human viruses for regulating translational stress responses.

Kaposi sarcoma (KS) is an AIDS-defining cancer and a significant global health challenge caused by KS-associated herpesvirus (KSHV). NGS-based approaches have profiled KS lesions in a minimal number of studies compared with other neoplastic diseases. Here we present a compiled and harmonized dataset of 131 KS and non-tumor cutaneous samples in the context of their predicted pathway activities, immune infiltrate, KSHV and HIV gene expression profiles, and their associated clinical data representing patient populations from Argentina, United States (USA), and Sub-Saharan Africa cohorts. RNA-seq data from 9 Argentinian KS lesions were generated and integrated with previously published datasets derived from the USA and sub-Saharan African cohorts from Tanzania, Zambia, and Uganda. An unsupervised analysis of 131 KS-related samples allowed us to identify four KS clusters based on their host and KSHV gene expression profiles, immune infiltrate, and the activity of specific signaling pathways. The compiled RNA-seq profile is shared with the research community through the UCSC Xena browser for further visualization, download, and analysis (https://kaposi.xenahubs.net/). These resources will allow biologists without bioinformatics knowledge to explore and correlate the host and viral transcriptome in a curated dataset of different KS RNA-seq-based cohorts, which can lead to novel biological insights and biomarker discovery.

Kaposi sarcoma is an angioproliferative disorder that affects the endothelial cells of the skin and mucous membranes. It is associated with human herpesvirus 8 (HHV-8), which is commonly found in immunocompromised individuals. However, it can also be present in immunocompetent patients. We report a case of Kaposi sarcoma (KS) in an 82-year-old immunocompetent male who is HIV-negative. There were no known risk factors for Kaposi sarcoma, such as a history of HIV or Mediterranean or Central/Eastern European and African ancestry. However, he did have brachytherapy-treated prostate cancer nineteen years ago. Biopsy of the skin lesions revealed vascular proliferation consistent with Kaposi sarcoma, and a diagnosis of an angiosarcoma-like Kaposi sarcoma subtype was made after multidisciplinary consultation. Given that this case shows that KS can develop in immunocompetent people who are HIV-negative, this form of KS may be a unique variation or subtype of classic Kaposi.

Kaposi sarcoma (KS) is a vascular tumour with four main clinical types—classic, endemic, iatrogenic, and epidemic—all linked to infection by human herpesvirus 8 (HHV-8). This retrospective cohort study assessed the relationship between demographic factors and clinical characteristics in 73 patients with biopsy-proven KS treated at a single dermatology centre between 2009 and 2023. Demographic and clinical data, including age, gender, birthplace, blood type, smoking, alcohol use, HIV status, tumour site, and disease stage, were collected and statistically analysed. Most patients were male (77%), with a mean age of 61 years, and the classic KS subtype predominated (86%). The majority (75%) had tumours localised to the extremities. HIV-positive status was diagnosed in 14% of cases and was strongly associated with non-extremity tumour location and increased visceral involvement. Notably, blood type showed a significant association with tumour localisation: 0Rh– and ARh– blood groups were less common in KS patients with extremity tumours. This is the first study to demonstrate a significant relationship between blood group and KS tumour site, introducing a novel epidemiological association. Smoking and alcohol consumption were each significantly linked to higher HIV positivity rates. Patients from the Mediterranean region had a higher frequency of HIV-positive KS, although birthplace did not correlate with disease stage. No associations were observed between gender and disease type. The study is limited by its retrospective design and missing data for certain variables, but it identifies potentially novel patterns—including a possible link between blood group and tumour location—and confirms known associations, such as HIV status with advanced disease. These findings underscore the complexity of KS presentation and suggest that demographic, clinical, and lifestyle factors may shape disease patterns. Prospective, multicentre studies are needed to validate these findings and guide personalised approaches to KS management.

Kaposi's sarcoma (KS) is a common cancer among people living with HIV and is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). While previous studies have linked the oral microbiome to KSHV infection and KS development, its role in KS progression remains poorly defined. We performed 16S rRNA gene sequencing targeting the V1-V2 and V3-V4 hypervariable regions to characterize the microbiome in 20 patients with AIDS-associated KS, including 10 with nonprogressive disease and 10 with progressive disease. Samples were obtained from three anatomical sites: oral cavity, peripheral blood, and tumor biopsies. The highest number of microbes were identified in the oral cavity at species, genus, and family levels. Beta diversity analysis revealed significant compositional differences in the oral microbiome between progressive and nonprogressive KS (p value = 0.044). Differential abundance analysis identified 16 species in the oral cavity associated with disease progression, compared to only three species in tumors and one in blood (p value < 0.05). Notably, Prevotella pallens and Megasphaera micronuciformis, both known producers of short-chain fatty acids, were significantly enriched in the oral microbiome of patients with progressive KS (log-fold changes = 2.8 and 2.4, respectively). Functional pathway inference revealed 39 differentially abundant microbial pathways in the oral cavity, including pathways related to denitrification, ubiquinone biosynthesis, and arginine metabolism (all p values < 0.05). Our findings provide the first evidence that specific oral microbiome alterations are associated with KS progression. The enrichment of short-chain fatty acid-producing bacteria and changes in microbial metabolic pathways may promote inflammation and KSHV lytic replication, offering potential mechanistic insights into KS pathogenesis and highlighting novel microbiome-based prognostic markers.

Outcome of systemic therapy in patients with advanced rare skin cancers: A retrospective multicenter DeCOG study of 209 patients.

Clinicopathologic and radio-genomic insights into hepatic epithelioid hemangioma: An illustrated review.

S3894 Colonic Kaposi Sarcoma Masquerading as Infectious Colitis in a Patient With AIDS

Remission of Recalcitrant Pyoderma Gangrenosum Following Chemotherapy for Iatrogenic Kaposi Sarcoma

Kaposi's Sarcoma-associated Herpesvirus encodes ORF74, a viral G protein-coupled receptor homologous to CXCR2, which plays a crucial role in Kaposi's Sarcoma development through its high basal signaling activity. Our cryoEM analysis of ORF74 in ligand-free, BRIL-fused ligand-free, and CXCL1/Gitrimer-bound forms elucidates its ligand-independent signaling activity. A widely open, static extracellular cavity facilitates ligand promiscuity by enabling dynamic access and diverse binding modes. Structural alterations in CWxP, E/DRY, and NPxxY micro-switches stabilize the active conformation, leading to constitutive signaling. Metadynamics simulations reveal a dynamic ensemble between local switch structures corresponding to the inactive and active states, supporting spontaneous activation. CXCR2-ORF74 chimeras highlight intracellular loops 2 and 3 as key modulators of basal and agonist-induced activity. This study defines the structural basis of ORF74's ligand promiscuity, spontaneous activation, and high basal signaling, providing insights into its role in viral oncogenesis.

We will explore the diagnostic similarities of spindle cell neoplasms and the attributed heuristics that lead to misdiagnosis biases. The biases explored will include availability bias and anchoring bias, with a discussion on the events leading to their formation. A 58-year-old African American male with a past medical history of well-controlled HIV presented to the dermatology clinic for a two-year history of several persistent skin nodules on his lower legs. One lesion on his left lateral calf, a 1.5 cm dome-shaped nodule with a centralized keratinous plug, was suspicious for squamous cell carcinoma (SCC), prompting a shave biopsy. The dermatopathology report identified the lesion as dermatofibrosarcoma protuberans (DFSP) with CD34 positivity and the patient was referred for Mohs Micrographic Surgery. Frozen sections during Mohs surgery revealed concern for an alternative diagnosis, which was then confirmed as Kaposi Sarcoma. This case highlights the susceptibility of dermatology to misdiagnosis. Availability bias in the clinical setting led to an inadequate biopsy method. Further anchoring bias then potentially influenced histologic interpretation and management decisions. Insufficient appreciation of Kaposi Sarcoma development in the setting of well-controlled HIV also further influenced the diagnosis rendered. Mohs Surgery evaluation allowed for de-biased clinical and histologic assessment, correcting diagnosis. Several overlying factors, such as time pressures, knowledge gaps, and technique limitations, create a reliance on cognitive heuristics. Recognizing these external pressures can help clinicians enhance diagnostic accuracy by systematically considering alternative diagnoses.