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The document is an interview with Professor Sabine Werner, a renowned figure in the field of dermatology and venereology. Professor Werner's career trajectory, research interests, mentors, achievements, and advice for young colleagues are discussed. She highlights her work in molecular dermatology, wound healing, and interdisciplinary collaborations. Professor Werner also shares her concerns about the challenges facing dermatology in the future and predicts breakthroughs in gene therapies and personalized medicine. [Extracted from the article]

Kaposi's sarcoma (KS) is a soft tissue lesion that resembles a hyperpigmented angiosarcoma and is typically associated with human herpesvirus 8 (HHV-8) infection. It is most frequently observed in immunocompromised patients, particularly those with AIDS, and is also referred to as HIV-associated Kaposi's sarcoma (AIDS-KS). The disease progresses rapidly, is challenging to manage, and has a high mortality rate. This case report presents a patient with AIDS-KS who experienced relapse after chemotherapy with anthracyclines. Subsequent chemotherapy with the same method had no significant effect. However, complete remission was achieved after the addition of a programmed cell death protein 1(PD-1) inhibitor, as confirmed by pathological biopsy. The PD-1 inhibitor was well-tolerated and had few adverse effects. It also helped to improve the immune reconstitution of the patient. The report highlights the remarkable efficacy of the PD-1 inhibitor in treating AIDS-KS. This provides case support for PD-1 inhibitors for AIDS-KS. [ABSTRACT FROM AUTHOR]

Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population‐based cancer registry data were used to identify cancer cases in both PLHIV and HIV‐negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2–36.6), non‐Hodgkin lymphoma (NHL) (1.6, 1.3–2.0), Hodgkin lymphoma (HL) (1.6, 1.1–2.4), cervical (2.3, 2.0–2.7), vulvar (4.0, 2.5–6.5), penile (3.0, 2.0–4.5), and eye cancers (2.2, 1.6–3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0–9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2–4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections. [ABSTRACT FROM AUTHOR]

The dermoscopic rainbow pattern (RP), also known as polychromatic pattern, is characterized by a multicolored appearance, resulting from the dispersion of polarized light as it penetrates various tissue components. Its separation into different wavelengths occurs according to the physics principles of scattering, absorption, and interference of light, creating the optical effect of RP. Even though the RP is regarded as a highly specific dermoscopic indicator of Kaposi's sarcoma, in the medical literature, it has also been documented as an atypical dermoscopic finding of other non-Kaposi skin entities. We aim to present two distinct cases—a pigmented basal cell carcinoma (pBCC) and an aneurysmatic dermatofibroma—that exhibited RP in dermoscopy and to conduct a thorough review of skin conditions that display RP, revealing any predisposing factors that could increase the likelihood of its occurrence in certain lesions. We identified 33 case reports and large-scale studies with diverse entities characterized by the presence of RP, including skin cancers (Merkel cell carcinoma, BCC, melanoma, etc.), adnexal tumors, special types of nevi (blue, deep penetrating), vascular lesions (acroangiodermatitis, strawberry angioma, angiokeratoma, aneurismatic dermatofibromas, etc.), granulation tissue, hypertrophic scars and fibrous lesions, skin infections (sporotrichosis and cutaneous leishmaniasis), and inflammatory dermatoses (lichen simplex and stasis dermatitis). According to our results, the majority of the lesions exhibiting the RP were located on the extremities. Identified precipitating factors included the nodular shape, lesion composition and vascularization, skin pigmentation, and lesions' depth and thickness. These parameters lead to increased scattering and interference of light, producing a spectrum of colors that resemble a rainbow. [ABSTRACT FROM AUTHOR]

Gammaherpesviruses are oncogenic pathogens that establish lifelong infections. There are no FDA-approved vaccines against Epstein–Barr virus or Kaposi sarcoma herpesvirus. Murine gammaherpesvirus-68 (MHV68) infection of mice provides a system for investigating gammaherpesvirus pathogenesis and testing vaccine strategies. Prime-boost vaccination with a replication-dead virus (RDV) that does not express the essential replication and transactivator protein (RTA) encoded by ORF50 (RDV-50.stop) protected against WT virus replication and reduced latency in C57BL/6 mice, and prevented lethal disease in Ifnar1−/− mice. To further improve the RDV vaccine and more closely model KSHV vaccine design, we generated an RDV lacking the unique M1-M4 genes and the non-coding tRNA-miRNA-encoded RNAs (TMERs) 6, 7, and 8 that collectively promote latency of MHV68 in vivo. Prime-boost vaccination of mice with RDV-50.stop∆M1-M4 elicited neutralizing antibodies and virus-specific CD8 T-cell responses in the lungs and spleens, the respective sites of acute replication and latency, that were comparable to RDV-50.stop vaccination. When challenged with WT MHV68, vaccinated mice exhibited a near-complete block of lytic replication and a reduction in latency and reactivation. We conclude that the unique M1-M4 genes and TMERs 6, 7, and 8, which are major determinants of WT MHV68 pathogenesis, are not required for eliciting protective immunity. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis. These viral proteins can modulate several cellular pathways, including the NF-κB and JAK/STAT pathways, which play essential roles in cell survival and inflammation. Epigenetic modifications further contribute to EBV- and KSHV-mediated cancerogenesis. Both EBV and KSHV manipulate host cell DNA methylation, histone modification, and chromatin remodeling, the interplay of which contribute to the elevation of oncogene expression and the silencing of the tumor suppressor genes. Immune factors also play a pivotal role in the development of cancer. The γ-herpesviruses have evolved intricate immune evasion strategies, including the manipulation of the major histocompatibility complex (MHC) and the release of cytokines, allowing infected cells to evade immune detection and destruction. In addition, a compromised immune system, such as in HIV/AIDS patients, significantly increases the risk of cancers associated with EBV and KSHV. This review aims to provide a comprehensive overview of the genetic, epigenetic, and immune mechanisms by which γ-herpesviruses drive cancerogenesis, highlighting key molecular pathways and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV), a γ-herpesvirus, is predominantly associated with Kaposi's sarcoma (KS) as well as two lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Like other herpesviruses, KSHV employs two distinct life cycles: latency and lytic replication. To establish a lifelong persistent infection, KSHV has evolved various strategies to manipulate the epigenetic machinery of the host. In latently infected cells, most viral genes are epigenetically silenced by components of cellular chromatin, DNA methylation and histone post-translational modifications. However, some specific latent genes are preserved and actively expressed to maintain the virus's latent state within the host cell. Latency is not a dead end, but the virus has the ability to reactivate. This reactivation is a complex process that involves the removal of repressive chromatin modifications and increased accessibility for both viral and cellular factors, allowing the activation of the full transcriptional program necessary for the subsequent lytic replication. This review will introduce the roles of epigenetic modifications in KSHV latent and lytic life cycles, including DNA methylation, histone methylation and acetylation modifications, chromatin remodeling, genome conformation, and non-coding RNA expression. Additionally, we will also review the transcriptional regulation of viral genes and host factors in KSHV infection. This review aims to enhance our understanding of the molecular mechanisms of epigenetic modifications and transcriptional regulation in the KSHV life cycle, providing insights for future research. [ABSTRACT FROM AUTHOR]

Kaposi's Sarcoma (KS) is a rare malignant tumor of blood vessel endothelial cells with a bleeding tendency. KS is relatively uncommon in the general population. However, its incidence significantly increases in people living with HIV. This article reports a rare case of nasal Kaposi's Sarcoma. Understanding the clinical presentation of this disease and its association with HIV is crucial for ENT doctors, emphasizing the importance of early diagnosis and treatment of KS. A case of Kaposi's sarcoma in the nasal cavity was reported. The patient had a history of AIDS and was being treated with highly active antiretroviral therapy (HAART). He presented with a 3-month history of progressive swelling on both sides of his nose. The pathology diagnosis was Kaposi's sarcoma. The lesion lessened after 3 times of chemotherapy. Nasal Kaposi's Sarcoma (KS) typically presents as purplish-red or purplish-black spots, patches, or lumps in the nasal cavity. Patients may experience local symptoms like nasal congestion, pain, or bleeding, and they may also exhibit systemic symptoms such as fever, fatigue, and weight loss. In patients without a history of immune suppression, consideration should be given to the possibility of HIV infection. Purely nasal KS often responds well to HAART treatment and may not require surgical excision. [ABSTRACT FROM AUTHOR]

In managing ulcerative colitis (UC), anti-tumour necrosis factor (TNF) agents are among the primary choices. Evidence suggests anti-TNF does not significantly increase malignancy risk (apart from lymphoma and melanoma), though uncertainties persist due to inconsistent long-term data. Kaposi's sarcoma (KS), induced by human herpesvirus type-8 (HHV-8), is a multifocal neoplasm linked to immunosuppressive therapies, primarily affecting the skin and gastrointestinal tract. KS cases during anti-TNF therapy for UC are anecdotal. We report a rare occurrence of KS in the setting of the long-term use of the standard maintenance dose of infliximab (initiated in 2010) in a 56-year-old male patient with UC diagnosed in 2001. The patient underwent restorative proctocolectomy with ileal J-pouch-anal anastomosis in 2002 and subsequently developed chronic antibiotic-dependent pouchitis. Given the secondary loss of response to infliximab, a switch to vedolizumab was performed. In April 2024, the patient reported the presence of a skin lesion on the right leg. Following surgery, a rhomboid-shaped skin area was removed, encompassing the irregular, greyish KS lesion. The histopathological analysis confirmed the diagnosis of patch-like KS. We continued vedolizumab due to its gut-selective profile. The patient is in clinical remission and under dermatological follow-up with no lesion recurrence. [ABSTRACT FROM AUTHOR]

"When you can measure what you are speaking about, and express it in numbers, you know something about it." is a famous quote attributed to Lord Kelvin. This sentiment puts viral load measurements at the center of virology. Viral load, or more precisely, DNA copy number measurements, are also used to follow infections with human herpesviruses, such as Kaposi sarcoma herpesvirus (KSHV) and Epstein–Barr Virus (EBV). EBV and KSHV are associated with human cancers, and determining their DNA copy numbers in the context of cancer prediction and progression on therapy is of fundamental scientific and translational interest. Yet, there is no generally accepted assay for KSHV DNA quantitation, and KSHV viral load is not used in clinical decision‐making. Here, we review the history of KSHV DNA detection assays, explore factors that affect sensitivity and specificity, and describe an automated, high‐throughput, real‐time quantitative polymerase chain reaction (PCR) assay for KSHV and EBV. In conjunction with a digital PCR assay using the same primer/probe combination, we describe how to determine the absolute KSHV genome copy numbers in plasma, peripheral blood mononuclear cells, saliva, and other easily accessible body fluids. [ABSTRACT FROM AUTHOR]

Simple Summary: This research is focused on Kaposi sarcoma (KS), a cancer occurring usually among children and adults living with HIV. Despite improvements in HIV treatments, KS remains common in eastern and central Africa. KS in children manifests in many different ways, from small skin lesions to cancer throughout the body. KS edema is a version of the disease where patients develop hard, wood-like skin lesions causing decreased mobility and quality of life. This study analyzes data from over a decade of treating pediatric KS in Malawi and aims to better describe the disease in children. The findings emphasize the chronic nature of KS edema, its propensity to relapse, its impact on survival, and the need for improved long-term management strategies to reduce relapses and progression. This research provides important insights into the unique biology and clinical presentation of KS in children, helping to guide future treatment approaches in resource-limited settings. Background/Objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children. Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital in Lilongwe, Malawi, focusing on children diagnosed with KS edema between 2010 and 2023. Results: We identified 52 children with KS edema, representing 27% of all patients with KS. Initial chemotherapy resulted in a clinical response in 92% of patients, but 46% experienced relapse or disease progression with a median time to first relapse of 12 months. Multiple progressions were common, with 31% of patients experiencing two or more events. Event-free survival at two years was 32%, dropping to 24% at five years, while overall survival was 73% at two years and 57% at five years. Relapse was more common among patients with KS edema versus those without it (relative risk = 2.1; 95%CI, 1.4–3.2; p < 0.001). Eight patients (15%) relapsed with visceral disease, five of whom originally presented with KS edema alone. Conclusions: Patients with KS edema have a unique, relapsing-remitting pattern of disease with a high risk of relapse relative to other forms of KS with subsequent long-term mortality, even after initial positive treatment responses. Late relapse and mortality with visceral disease are possible even among children presenting initially with KS edema alone. Children with KS edema require long-term follow-up, and novel treatment approaches tailored towards preventing frequent relapse are needed. [ABSTRACT FROM AUTHOR]

Skin cancer, the most common cancer in the United States, has been well-described in the literature to be associated with environmental factors including ultraviolet (UV) radiation. However, the effect of chronic viral infections on risk of skin cancer development, particularly in individuals co-infected with Human Immunodeficiency Virus (HIV) and Hepatitis B or C Viruses (HBV/HCV), has yet to be elucidated. This systematic review aims to be one of the first to consolidate existing literature and examine the relationship between skin cancer and HIV/HBV and HIV/HCV co-infections. We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, Embase, Cochrane CENTRAL, and Web of Science databases for studies published from inception to March 26, 2024. Inclusion criteria for studies included only those reporting on HBV and/or HCV in people living with HIV (PLWH). Five studies were ultimately included for analysis. The review identified multiple non-melanoma skin cancers (NMSC) and cutaneous adnexal carcinomas in HIV/HCV or HIV/HBV co-infected patients. Notably, Pilomatrical carcinomas were observed in co-infected individuals. Sarcomas including Kaposi sarcoma and low-grade fibroblastic sarcoma were also linked to HIV/HCV or HIV/HBV infections. However, the studies primarily focused on specific types of cancers without elucidating the underlying mechanisms for the association between HIV/HCV/HBV infection and sarcoma development. In summary, this review suggests a potential link between HIV/HCV and HIV/HBV co-infection and certain types of skin cancer, namely adnexal carcinomas. Further research is crucial to determine the underlying mechanisms, explore the association with different skin cancer types, and identify effective prevention and treatment strategies for co-infected individuals. [ABSTRACT FROM AUTHOR]

De novo or viral reactivation cancers are a major cause of morbidity and mortality in the solid organ transplant (SOT) population. Primary sclerosing cholangitis (PSC) is an aggressive disease which can lead to cholestatic liver damage and cirrhosis. PSC often cooccurs with inflammatory bowel disease (IBD). Here, we describe the case of a 28‐year‐old male with PSC along with poorly controlled IBD who underwent a liver transplant and developed colonic Kaposi sarcoma (KS). Our case highlights the importance of adequate pretransplant screening for endemic viruses, high clinical suspicion for KS in the setting of difficult‐to‐control colitis, and early multidisciplinary involvement. [ABSTRACT FROM AUTHOR]

ABSTRACT Kaposi sarcoma is a human herpesvirus 8–associated angio‐proliferative tumor arising from lymphatic endothelial cells. Four clinical subtypes are known: classic, epidemic, endemic, and iatrogenic. The development of Kaposi sarcoma and lymphedema may be interlinked, where each condition could potentially support the progression of the other. Post‐mastectomy lymphedema is a commonly recognized complication following radical mastectomy. Angiosarcoma is the most frequently reported neoplasm in such a situation. We present a 72‐year‐old female who developed Kaposi sarcoma on the same side of mastectomy 9 years following her initial diagnosis and treatment for cancer breast. The diagnosis of Kaposi sarcoma was based on the histopathologic findings and was confirmed with immunohistochemical staining for human herpes virus 8 and D2‐40. Lymphedema may be associated with local immune suppression manifested in the form of defective cell–mediated immunity and antigen‐presenting cell migration defect which may facilitate development of neoplasms. It is important to differentiate Kaposi sarcoma from other vascular tumors which may have a much worse prognosis. Patients with lymphedema should receive appropriate management and undergo long‐term follow‐up for early detection of any potential malignancies. [ABSTRACT FROM AUTHOR]

The article discusses the dermoscopic characterization of angiolymphoid hyperplasia in patients with skin of color, focusing on a case series of six patients. The study highlights the usefulness of dermoscopy in diagnosing this rare vascular disorder, noting variations in findings compared to lighter skin phenotypes. The article provides detailed dermoscopic findings, clinical profiles, and histological correlations, emphasizing the importance of recognizing specific features for accurate diagnosis. Additionally, the study compares findings between early and late lesions, offering insights into the diagnostic challenges and differential diagnoses associated with angiolymphoid hyperplasia. [Extracted from the article]

Background Kaposi sarcoma (KS) is a marker of advanced HIV disease; it is still the most frequent AIDS-associated malignancy in Mexico despite universal access to antiretroviral therapy, reflecting a gap in early HIV diagnosis. Methods The objectives of the study were to describe people with HIV with KS who died within 30 days of admission at INCan (National Cancer Institute) and to quantify resources and years of life lost (YLL). We collected demographic data, HIV-related variables, all diagnostic and therapeutic procedures, hospitalizations, and estimated YLL and disability-adjusted life years. Results Eighteen (6.7%) people with HIV with KS from 270 patients admitted at INCan from 2014 to 2021 were included. The median age was 31 years (IQR 27–36), and the median days from admission to death and from HIV diagnosis to death were 15 (IQR, 6–24) and 73 (IQR, 30–857), respectively. Upon admission, the median HIV viral load was 314 476 copies/mL (IQR, 140 709–695 613); CD4+ T cells, 93 cells/mL (IQR 35–124); and CD4/CD8 ratio, 0.08 (IQR, 0.06–0.12). Coinfections were diagnosed in 14 (77.7%) patients. The average expenditure per patient was US $7685.99 USD, and the total YLL was 737.4 with a median 42 years (IQR, 37.7–47) per patient. The total care cost was US $183 947.48, equivalent to a screening program in key populations, which would have allowed the early detection of 1227 cases and saved 8410 disability-adjusted life years. Conclusions Reinforcement of early HIV infection detection in key population programs should be prioritized to reduce KS-associated deaths and YLL and for rational use of health budgets. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is a cutaneous neoplasm of endothelial origin. The causative agent is the human herpes virus-8 (HHV-8) which, combined with an immune system impairment, causes cell proliferation. To date, high-quality evidence and treatment recommendations for the management of KS are confined to the acquired immune deficiency syndrome (AIDS)-related KS, while the clinical approach to the treatment of classic KS (CKS) is based on small retrospective case series and the experience of clinicians in selected referral centers. Materials and Methods: A search of the English literature was conducted through PubMed/MEDLINE databases for studies regarding CKS diagnosis, staging, and treatment, published between January 1990 and September 2023. Results: Overall, 122 out of 565 articles were selected. Based on the results of this literature review, we proposed indications regarding the recommended flow chart for diagnosis, staging, and follow-up of patients with CKS. We assess available evidences regarding topic, locoregional, and systemic treatments of CKS. We also provide a focus on novel treatment strategies and therapeutic approaches currently under evaluation in clinical trials. Conclusion: CKS is a rare disease and its management requires a multidisciplinary assessment. Treatment in referral centers and enrolment in clinical trials might impact on outcomes. [ABSTRACT FROM AUTHOR]

Background: Human herpes virus 8 (HHV‐8) or Kaposi sarcoma herpesvirus (KSHV) is an opportunistic oncovirus that causes multiple pathologic entities. Methods: We present a case of fatal HHV‐8‐associated multisystem illness with disseminated Kaposi sarcoma and HHV8‐associated lymphoproliferative disorder with systemic inflammation. We conducted a narrative review of the literature on HHV‐8 in transplantation with a goal of illuminating the spectrum of HHV‐8‐associated diseases in this vulnerable population, modes of disease transmission, and the potential role for donor and recipient screening. Results: HHV‐8‐associated KS, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KSHV inflammatory cytokine disorder (KICS) may affect transplant recipients; with the exception of KS, these conditions are rare but carry high morbidity and mortality. Conclusion: HHV‐8‐associated diseases have diverse and protean manifestations in transplant recipients, with potentially fatal outcomes. HHV‐8 seroprevalence among organ donors and the magnitude of risk for donor‐derived HHV‐8 infection or clinically significant disease remain unknown and require further study. [ABSTRACT FROM AUTHOR]

Birds, especially the chick and hen, have been important biomedical research models for centuries due to the accessibility of the avian embryo and the early discovery of avian viruses. Comprehension of avian tumor virology was a milestone in basic cancer research, as was that of non-viral genesis, as it enabled the discovery of oncogenes. Furthermore, studies on avian viruses provided initial insights into Kaposi's sarcoma and EBV-induced diseases. However, the role of birds in human carcinogenesis extends beyond the realm of virology research. Utilization of CAM, the chorioallantoic membrane, an easily accessible extraembryonic tissue with rich vasculature, has enabled studies on tumor-induced angiogenesis and metastasis and the efficient screening of potential anti-cancer compounds. Also, the chick embryo alone is an effective preclinical in vivo patient-derived xenograft model, which is important for the development of personalized therapies. Furthermore, adult birds may also closely resemble human oncogenesis, as evidenced by the laying hen, which is the only animal model of a spontaneous form of ovarian cancer. Avian models may create an interesting alternative compared with mammalian models, enabling the creation of a relatively cost-effective and easy-to-maintain platform to address key questions in cancer biology. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi sarcoma-associated herpesvirus (KSHV) is associated with lymphoproliferative disorders, including primary effusion lymphoma and multicentric Castleman disease. KSHV expresses viral proteins that aid in the evasion of antiviral immune responses and manipulate host factors and signaling to promote cell survival. By altering the cell environment, KSHV contributes to lymphomagenesis. Approximately 15–20% of cancers are caused by viruses. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is an oncogenic virus that is the etiologic agent of not only Kaposi sarcoma but also the lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV can infect a broad tropism of cells, including B lymphocytes, wherein KSHV encodes specific viral proteins that can transform the cell. KSHV infection precedes the progression of PEL and MCD. KSHV establishes lifelong infection and has two phases of its lifecycle: latent and lytic. During the latent phase, viral genomes are maintained episomally with limited gene expression. Upon sporadic reactivation, the virus enters its replicative lytic phase to produce infectious virions. KSHV relies on its viral products to modulate host factors to evade immune detection or to co-opt their function for KSHV persistence. These manipulations dysregulate normal cell pathways to ensure cell survival and inhibit antiviral immune responses, which in turn, contribute to KSHV-associated malignancies. Here, we highlight the known molecular mechanisms of KSHV that promote lymphomagenesis and how these findings identify potential therapeutic targets for KSHV-associated lymphomas. [ABSTRACT FROM AUTHOR]

Background: Preferentially expressed antigen in melanoma (PRAME) has been extensively studied in cutaneous melanocytic tumors and has proven valuable as a diagnostic adjunct in routine dermatopathology practice. However, its expression in cutaneous vascular neoplasms, particularly angiosarcomas (AS), remains largely unexplored. Methods: To further explore PRAME expression in cutaneous AS, 18 cases of post‐irradiation and 13 cases of primary cutaneous AS were evaluated for PRAME. For comparison, sections from 11 deep soft tissue/visceral AS, 10 Kaposi sarcomas, 8 microvenular hemangiomas, 7 infantile hemangiomas, 8 atypical vascular lesions, 6 epithelioid hemangioendotheliomas, 6 pyogenic granulomas, 6 papillary endothelial hyperplasias, 6 epithelioid hemangiomas, 3 capillovenous malformations, 3 hobnail hemangiomas, 2 spindle cell hemangiomas, 2 pseudomyogenic hemangioendotheliomas, and 2 composite hemangioendotheliomas were also retrieved. Results: Overall, 22 of 31 (70.9%; 12 post‐irradiation and 10 primary) cutaneous AS were positive for PRAME. In contrast, only 1 of 11 (9.1%) deep soft tissue/visceral AS showed diffuse and strong PRAME nuclear staining. All other tumor types were negative for PRAME, except for 5 of 7 (71.4%) infantile hemangiomas, which demonstrated rare (<5%; four cases) and 1+ (5–25%; one case) nuclear staining. Conclusions: In this study, we have demonstrated frequent nuclear PRAME expression in cutaneous AS. PRAME immunohistochemistry may serve as a valuable additional marker in selected clinical settings. [ABSTRACT FROM AUTHOR]

In managing ulcerative colitis (UC), anti-tumour necrosis factor (TNF) agents are among the primary choices. Evidence suggests anti-TNF does not significantly increase malignancy risk (apart from lymphoma and melanoma), though uncertainties persist due to inconsistent long-term data. Kaposi’s sarcoma (KS), induced by human herpesvirus type-8 (HHV-8), is a multifocal neoplasm linked to immunosuppressive therapies, primarily affecting the skin and gastrointestinal tract. KS cases during anti-TNF therapy for UC are anecdotal. We report a rare occurrence of KS in the setting of the long-term use of the standard maintenance dose of infliximab (initiated in 2010) in a 56-year-old male patient with UC diagnosed in 2001. The patient underwent restorative proctocolectomy with ileal J-pouch-anal anastomosis in 2002 and subsequently developed chronic antibiotic-dependent pouchitis. Given the secondary loss of response to infliximab, a switch to vedolizumab was performed. In April 2024, the patient reported the presence of a skin lesion on the right leg. Following surgery, a rhomboid-shaped skin area was removed, encompassing the irregular, greyish KS lesion. The histopathological analysis confirmed the diagnosis of patch-like KS. We continued vedolizumab due to its gut-selective profile. The patient is in clinical remission and under dermatological follow-up with no lesion recurrence.

Abstract The co‐occurence of multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) represents a rare clinical entity, mostly observed in individuals infected with the human immunodeficiency virus (HIV). Human herpesvirus 8 (HHV‐8) is attributed a crucial etiological role in both conditions. This study presents the case of a 75‐year‐old woman who manifested an angiomatous lesion on the right thigh and erythematous firm plaques on the trunk and limbs, accompanied by asthenia, weight loss, and recurrent febrile episodes. Serological markers for HIV yielded negative results. Contrast‐enhanced computed tomography (CT) and fluorine‐18 fluorodeoxyglucose positron emission tomography (18 F FDG PET/CT) revealed multiple enlarged and intensely hypermetabolic lymph nodes in the supraclavicular, cervical, thoracic, and abdominopelvic regions. Subsequent excisional biopsy and immunohistochemical analysis confirmed the diagnosis of HIV‐negative HHV8‐positive MCD coexisting with KS.

Introduction. According to the European Cancer Information System, melanoma is the sixth most diagnosed cancer in Europe (following breast, colorectal, prostate, lung, and bladder cancer) and ranks among the top 20 most common causes of cancer-related death. The diagnosis of melanoma can be a clinical challenge due to the variety of signs and symptoms, ranging from small, asymptomatic lesions with slow progression to large, painful tumors with rapid growth. In this paper, we will report an exceptional case of cutaneous melanoma with an atypical presentation in a patient with no personal or family history of skin cancer. Case presentation. We present the case of an 85-year-old patient who presented to our dermatology clinic with multiple nodular lesions on her right calf, extending to her thigh as isolated lesions. These violaceous lesions varied in size and displayed signs of bleeding, fibrin deposits, and purulent, foul-smelling discharge. The patient reported a fivemonth history of rapid tumor progression. The initial presumptive diagnosis was Kaposi's sarcoma; however, the biopsy ruled out this diagnosis, revealing the presence of malignant melanoma. Given the extensive locoregional spread and invasion of deep structures, the patient was transferred to palliative care. Conclusions. Melanoma is an aggressive form of cancer that can rapidly progress, often presenting with atypical clinical manifestations or mimicking other skin conditions. When the clinical presentation deviates from the classic patterns, a biopsy is considered the gold standard for guiding the clinician's subsequent approach. It provides valuable diagnostic information and aids in determining the prognosis as well as the appropriate therapeutic course.

Background An improved understanding of oral Kaposi sarcoma–associated herpesvirus (KSHV) viral dynamics could provide insights into transmission risk and guide vaccine development. Methods We evaluated KSHV oral shedding dynamics in Ugandan adults stratified by Kaposi sarcoma (KS) and human immunodeficiency virus (HIV) status. Participants were followed for ≥4 weeks, with daily home oral swab collection to quantify KSHV using polymerase chain reaction. Shedding rates were defined by number of days with KSHV DNA detected divided by total days with swabs and compared by group using hurdle models. Results Two hundred ninety-five participants were enrolled; median age was 35 years (range, 18–71 years), and 134 (45%) were male. KSHV was detected more frequently among participants with KS (HIV positive [HIV+]/KS+, 56/76 [74%]; HIV negative [HIV−]/KS+, 9/18 [50%]) than those without KS (HIV+/KS−, 36/125 [29%]; HIV−/KS−, 16/76 [21%]); odds of shedding did not differ significantly by HIV status. Among participants with KSHV detected, shedding rates did not differ significantly by group. Median per-participant viral loads among positive samples were lowest in HIV+/KS+ (3.1 log10 copies/mL) and HIV−/KS+ (3.3 log10 copies/mL) participants relative to HIV+/KS− (3.8 log10 copies/mL) and HIV−/KS− (4.0 log10 copies/mL) participants. All groups had participants with low viral load intermittent shedding and participants with high viral load persistent shedding. Within each group, individual KSHV shedding rate positively correlated with median KSHV log10 copies/mL, and episode duration positively correlated with peak viral load. Conclusions Oral KSHV shedding is highly heterogeneous across Ugandan adults with and without KS and HIV. Persistent shedding is associated with higher median viral loads regardless of HIV and KS status. [ABSTRACT FROM AUTHOR]

The Herpesviridae include the Epstein–Barr Virus (EBV) and the Kaposi Sarcoma-associated Herpesvirus (KSHV), both of which are oncogenic gamma-herpesviruses. These viruses manipulate host cellular mechanisms, including through ubiquitin-mediated pathways, to promote viral replication and oncogenesis. Ubiquitin, a regulatory protein which tags substrates for degradation or alters their function, is manipulated by both EBV and KSHV to facilitate viral persistence and cancer development. EBV infects approximately 90% of the global population and is implicated in malignancies including Burkitt lymphoma (BL), Hodgkin lymphoma (HL), post-transplant lymphoproliferative disorder (PTLD), and nasopharyngeal carcinoma. EBV latency proteins, notably LMP1 and EBNA3C, use ubiquitin-mediated mechanisms to inhibit apoptosis, promote cell proliferation, and interfere with DNA repair, contributing to tumorigenesis. EBV's lytic proteins, including BZLF1 and BPLF1, further disrupt cellular processes to favor oncogenesis. Similarly, KSHV, a causative agent of Kaposi's Sarcoma and lymphoproliferative disorders, has a latency-associated nuclear antigen (LANA) and other latency proteins that manipulate ubiquitin pathways to degrade tumor suppressors, stabilize oncogenic proteins, and evade immune responses. KSHV's lytic cycle proteins, such as RTA and Orf64, also use ubiquitin-mediated strategies to impair immune functions and promote oncogenesis. This review explores the ubiquitin-mediated interactions of EBV and KSHV proteins, elucidating their roles in viral oncogenesis. Understanding these mechanisms offers insights into the similarities between the viruses, as well as provoking thought about potential therapeutic targets for herpesvirus-associated cancers. [ABSTRACT FROM AUTHOR]

The article discusses a case of iatrogenic Kaposi sarcoma (KS) in a Hispanic patient with rheumatoid arthritis (RA) due to treatment with Janus kinase (JAK) and tumor necrosis factor (TNF) α inhibitors. The patient developed disseminated lesions after starting methotrexate, baricitinib, and deflazacort, which worsened with golimumab. Treatment involved discontinuing immunosuppressive medications and using doxorubicin, peginterferon alfa‐2a, and valganciclovir, resulting in lesion regression. The study also reviews similar cases of RA patients developing iatrogenic KS from JAK and TNF‐α inhibitors, emphasizing the importance of considering this condition in autoimmune disease treatment. [Extracted from the article]

Objective: This study aims to examine the expression of androgen receptor (AR) and estrogen receptor (ER) in patients with classic Kaposi's sarcoma (CKS) in Xinjiang, as well as to assess the serum levels of sex hormones in these patients. The objective is to explore potential new directions and targets for diagnosing and treating CKS in Xinjiang. Methods: The case group comprised 35 patients diagnosed with CKS who presented at our hospital from 2014 to 2021. The control group consisted of 35 patients with pyogenic granuloma (PG) who visited the hospital during the same period, selected using propensity score matching (PSM). Immunohistochemistry was used to detect AR, human herpesvirus type 8 (HHV‐8), and ER in paraffin‐embedded tissue samples from patients diagnosed with CKS and PG. Additionally, enzyme‐linked immunosorbent assay (ELISA) was used to quantitatively measure serum sex hormone levels in the 35 patients with CKS and 35 patients with PG. Results: AR expression was relatively weak in both the CKS and PG groups, with the PG group exhibiting a slightly stronger expression than the CKS group. Conversely, the expression of ER was significantly higher in the CKS group compared to the PG group (p < 0.05). Additionally, serum testosterone (T) levels were elevated in the CKS group, while serum estradiol (E2) levels were higher in the PG group (p < 0.05). Conclusion: Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS. [ABSTRACT FROM AUTHOR]

The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings. [ABSTRACT FROM AUTHOR]

Paclitaxel is one of the most widely utilized anticancer drug. It displays a range of antitumor action, particularly against ovarian cancer, urologic malignancies, head tumor, and Kaposi's sarcoma. However, due to its highly lipophilic nature, poor fluid dissolvability of less 0.01 mg/mL and lack of ionizing functionalities which may enhance its solubility, there are substantial challenges associated with Paclitaxel delivery. Paclitaxel exhibited promising effects when formulated in combination with ethanol and Cremophor EL, as Taxol®. However, it is associated with various side effects, including hypersensitivity, hypotension, and peripheral neuropathy. The albumin-based Paclitaxel, Abraxane®, is a superior alternative to Taxol® as it diminishes the side effects related to Cremophor EL. Abraxane® is regarded as the gold standard for cancer treatment, but its 21% response rate suggests that more research is needed. Furthermore, the large-scale clinical use of this drug has faced considerable delay because of the absence of suitable delivery vehicles. Therefore, necessitates is the development of an alternate form of Paclitaxel that has both superior aqueous solubility as well as fewer side-effects. During the last decade, various methodologies have been explored to improve Paclitaxel's solubility with the help of co-solvents and inclusion complexes. Additionally, various methodologies report of passive targeting of cancer cells using nanoparticles, nanosuspensions, Rotaxane (a mechanically interlocked molecular system), liposomes, micelles, emulsions, gels, pastes, etc. Herein, we have comprised a brief report on various delivery techniques for Paclitaxel with improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to describe the prevalence of high‐risk human papillomavirus (HR‐HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. Setting: Referral tertiary care hospital for adult patients with cancer. Methods: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high‐resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. Results: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32‐47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non‐Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR‐HPV infection was 89% (n=138) (95% CI 83–93) with at least one HR‐HPV infection, and 62% (96) had coinfection with at least two types; the median HR‐HPV types of coinfection were 3 (IQR 2–4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8–49.3), HPV 18 was 74 (47.7%, 95% CI 39.9–55.7) and with both 35 (22.6%). Some 59 patients (38%) had high‐grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low‐grade squamous intraepithelial lesions (LSIL). The prevalence of HR‐HPV and HSIL among patients aged ≤35 and >35 years was the same. Conclusions: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR‐HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy. [ABSTRACT FROM AUTHOR]

Objectives. Emmprin (CD147/BSG) protein is estimated to play a key role in cell migration and chemoresistance in viral carcinogenesis. However, there are very limited studies investigating the CD147 in the oncogenesis of Kaposi's sarcoma-associated herpesvirus. This study aims to reveal the relationship between CD147 expression with histopathological parameters, disease pattern, and recurrence in Kaposi's sarcoma (KS). Methods. The study included 67 patients diagnosed with KS between January 1982 and September 2023. Clinical and histopathological features were analyzed retrospectively. HHV-8, CD31, and CD147 expressions were evaluated by immunohistochemistry. Results. Sixteen (24%) female and 51 (76%) male patients with median age of 64 (10-86) were included in the study. CD147 was positive in 57 (85%) cases and associated with nodular pattern (P =.001), presence of solid/fibrosarcomatous area (P =.005), and high mitotic activity (P =.035). The disease relapsed in 17 (27%) of the 63 patients with median 2 (0-12) years follow-up. While a 5-year relapse-free survival was 48.5% in the CD147 diffuse positive group, it was 83.4% in focal positive and 100% in negative cases (P =.029). Conclusion. Our study exhibited the relationship between CD147 overexpression and recurrence in KS, but the inhomogeneity of the treatment groups and the small number of patients should also be considered. These findings may provide insight into the pathogenesis of KS and the development of targeted therapies in the future. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-associated Kaposi's sarcoma (HIV-KS) is a well-documented vascular tumor with a pathogenesis involving human herpesvirus-8 (HHV-8) infection. While antiretroviral therapy (ART) and chemotherapy are effective for treating most KS cases, some become refractory. In this report, we present a case of a 58-year-old man with refractory HIV-KS treated with ART and chemotherapy. Chemotherapy was eventually discontinued due to an adverse reaction, and the patient presented with painful plantar lesions that impaired ambulation. With the exclusion of visceral metastases, localized radiotherapy was administered, which resulted in significant cosmetic and functional improvements. The patient regained ambulation and lived independently, receiving additional radiotherapy as needed. This case underscores the potential use of radiotherapy for the treatment of ART-resistant KS, particularly when the patient is unresponsive to conventional chemotherapy. It also highlights the need for future research in this area. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions. [ABSTRACT FROM AUTHOR]

Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are no cures for KSHV infection. KSHV establishes biphasic lifelong infections. During the lytic phase, new genomes are replicated by seven viral DNA replication proteins. The processivity factor's (PF‐8) functions to tether DNA polymerase to DNA, so new viral genomes are efficiently synthesized. PF‐8 self‐associates, interacts with KSHV DNA replication proteins and the viral DNA. Inhibition of viral DNA replication would diminish the infection within a host and reduce transmission to new individuals. In this review we summarize PF‐8 molecular and structural studies, detail the essential protein‐protein and nucleic acid interactions needed for efficient lytic DNA replication, identify future areas for investigation and propose PF‐8 as a promising antiviral target. Additionally, we discuss similarities that the processivity factor from Epstein‐Barr virus shares with PF‐8, which could promote a pan‐herpesvirus antiviral therapeutic targeting strategy. [ABSTRACT FROM AUTHOR]

Backgrounds: Kaposi sarcoma (KS) is a unique form of cancer with epidemiological characteristics distinct from those of other solid cancers. While common risk factors including alcohol consumption, smoking, and metabolic disorders have been well studied in various cancers, their relationship with KS remains unclear. Methods: This study used a cohort approach with adults without AIDS, utilizing data from the National Health Insurance Service in South Korea. This study examined various conventional cancer-related risk factors related to the incidence of KS, including psoriasis. Results: Alcohol consumption, smoking, body mass index, diabetes mellitus, hypertension, hypercholesterolemia, and regular exercise were not significantly associated with the incidence of KS. Additionally, older age and male sex were associated with a higher incidence of KS. KS risk was increased in pathological conditions such as psoriasis and proteinuria, which require immunosuppressive medication. Conclusions: Our study suggests that traditional cancer-related risk factors may not play a significant role in the pathogenesis of KS, unlike other cancers. This, in turn, emphasizes the importance of immunosuppression and HHV-8 infection in the development of KS. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the efficacy of radiotherapy for skin lesions in classic Kaposi's sarcoma. A retrospective analysis was performed. Response after radiotherapy was defined as follows: Complete response indicated no clinically detectable skin lesions and no symptoms. Partial response was defined as a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was defined as the appearance of new lesions within a previously irradiated field. The overall response rate was 100%. The efficacy of radiotherapy was evident, even in cases involving disseminated lesions. Further research on the optimal dose and fractionation is deemed necessary. Objectives: Classic Kaposi's sarcoma (CKS) is a rare malignancy with diverse clinical presentations, lacking a standard treatment. While localized therapies are commonly used for symptomatic lesions, radiotherapy (RT) has demonstrated effectiveness. This study aims to evaluate the efficacy of RT for treating skin lesions in CKS. Methods: A retrospective analysis was conducted on patients with KS treated between April 2012 and January 2024. In total, 69 lesions in 16 patients were included. Treatment response was defined as follows: complete response (CR) indicated the absence of clinically detectable skin lesions and symptoms; partial response (PR) was a reduction in lesion height by more than half or a lighter lesion color compared to before treatment. In-field recurrence was the appearance of new lesions within a previously irradiated field. Logistic regression analysis was used to investigate factors influencing response and in-field recurrence. Results: The median follow-up period was 52 months (range, 3–138 months). The overall response rate was 100%, with 92.8% of the patients achieving CR and 7.2% receiving PR. PR was observed in three patients with five lesions, all of which remained stable. In-field recurrence occurred in two patients with initially advanced disease, and all recurrent lesions responded to RT. No variables were significantly associated with response or in-field recurrence. Conclusions: RT for CKS showed a 100% response rate, with complete symptom relief in all cases. The effectiveness of RT was evident, even in cases involving disseminated lesions. Further research is needed to determine the optimal RT dose and fractionation. [ABSTRACT FROM AUTHOR]

Although extensively studied in cutaneous epithelial neoplasms, the TRPS1 immunoreactivity in cutaneous mesenchymal neoplasms and tumors of uncertain differentiation (CMNTUDs), such as atypical fibroxanthoma (AFX), remains largely unexplored. We assessed TRPS1 immunoreactivity in 135 CMNTUDs, comprising 46 fibrohistiocytic/fibroblastic tumors, 28 vascular tumors, 24 peripheral nerve sheath tumors (PNSTs), 21 tumors of uncertain differentiation, and 16 smooth muscle tumors. Additionally, we included selected cases of melanoma with spindled cell morphology or desmoplastic features (n = 9) and sarcomatoid squamous cell carcinoma (SSCC) (n = 5) to compare TRPS1 expression patterns with those of AFX. TRPS1 expression was prevalent in dermatofibromas (24/24), leiomyomas (8/8), AFXs/pleomorphic dermal sarcoma (PDS) (20/21), dermatofibrosarcomas protuberans (14/22), and leiomyosarcomas (6/8). It was uncommon in angiosarcomas (3/20), Kaposi sarcomas (2/8), and neurofibromas (5/17) and absent in perineuriomas (0/2). AFXs/PDS exhibited the highest median H-score of 240, contrasting with minimal TRPS1 immunoreactivity in vascular neoplasms and PNSTs, with median H-scores consistently below 10. Significant differences in H-score were observed between AFXs/PDS and angiosarcomas (p < 0.001), melanomas (p < 0.001), and leiomyosarcomas (p = 0.029). However, no significant difference was found compared to SSCCs, suggesting limited discriminatory power of TRPS1 in this context. This study sheds light on TRPS1 expression patterns in a subset of CMNTUDs, extending beyond prior studies primarily focused on epithelial tumors, while underscoring potential pitfalls associated with TRPS1 immunohistochemistry. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV) is a cancer-causing virus that establishes life-long infection. KSHV is implicated in the etiology of Kaposi's sarcoma, and a number of rare hematopoietic malignancies. The present study focuses on the KSHV open reading frame 20 (ORF20), a member of the conserved herpesvirus UL24 protein family containing five conserved homology domains and a conserved PD-(D/E)XK putative endonuclease motif, whose nuclease function has not been established to date. ORF20 encodes three co-linear protein isoforms, full length, intermediate, and short, though their differential functions are unknown. In an effort to determine the role of ORF20 during KSHV infection, we generated a recombinant ORF20-Null KSHV genome, which fails to express all three ORF20 isoforms. This genome was reconstituted in iSLK cells to establish a latent infection, which resulted in an accelerated transcription of viral mRNAs, an earlier accumulation of viral lytic proteins, an increase in the quantity of viral DNA copies, and a significant decrease in viral yield upon lytic reactivation. This was accompanied by early cell death of cells infected with the ORF20-Null virus. Functional complementation of the ORF20-Null mutant with the short ORF20 isoform rescued KSHV production, whereas its endonuclease mutant form failed to enhance lytic reactivation. Complementation with the short isoform further revealed a decrease in cell death as compared with ORF20-Null virus. Finally, expression of IL6 and CXCL8, previously shown to be affected by the hCMV UL24 homolog, was relatively low upon reactivation of cells infected with the ORF20-Null virus. These findings suggest that ORF20 protein, with its putative endonuclease motif, promotes coordinated lytic reactivation for increased infectious particle production. [ABSTRACT FROM AUTHOR]

Kaposi's Sarcoma (KS) is a malignant vascular tumor commonly seen in immunocompromised individuals, particularly patients with acquired immunodeficiency syndrome. Lung transplant recipients are at high risk of developing KS due to a strong immunosuppressive regimen that can lead to donor-derived infection or reactivation of recipient human herpesvirus 8, the causative organism for KS. In this overview, we describe 2 lung transplant recipients who developed pulmonary KS with poor outcomes, reviewing the diagnosis, bronchoscopy findings, and treatment and surveillance strategies for pulmonary KS. [ABSTRACT FROM AUTHOR]

Background: Tetracyclines are a class of broad-spectrum antibiotics favored by dermatologists. Over the last decade, the clinical efficacy of tetracyclines has expanded into various dermatoses. Summary: This review tries to encompass the possible indications of tetracycline in the field of dermatology and possible mechanisms of action. This comprehensive review encompasses all possible indications of tetracyclines besides acne vulgaris and rosacea: hidradenitis suppurativa, autoimmune bullous dermatoses, vitiligo, alopecia, prurigo pigmentosa, granulomatous dermatoses, Kaposi's sarcoma, cold urticaria, atopic dermatitis, scrub typhus, scarring, and miscellaneous dermatoses. We also focus on the recently approved sarecycline, a third-generation narrow-spectrum tetracycline, and its clinical efficacy and potential impact on the microbiome. Our review provides a better understanding of this extremely familiar drug class and encourages its use in a wider spectrum of dermatologic diseases and symptoms. Key Messages: This study comprehensively reviewed the current literature on potential indications of tetracyclines in the field of dermatology. Plain Language Summary: Despite their initial approval as antibiotics, the clinical usage of tetracyclines by dermatologists has been expanded to dermatoses with a predominantly inflammatory pathophysiology. The potential indications of tetracyclines in the field of dermatology include not only acne and rosacea but also hidradenitis suppurativa, autoimmune bullous dermatoses, vitiligo, alopecia, prurigo pigmentosa, granulomatous dermatoses, Kaposi's sarcoma, cold urticaria, atopic dermatitis, scrub typhus, scarring, and miscellaneous dermatoses. Sarecycline has shown promising results in rosacea in addition to its approval for acne vulgaris with a narrow antimicrobial spectrum and less impact on the microbiome, indicating possible superiority over other tetracyclines in terms of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background Reemergence of human herpesvirus 8 (HHV-8)–induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge because they already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls respectively). Methods Plasma, peripheral blood mononuclear cell, and skin tissues were obtained from 11 HIV KS and 11 cKS patients and 2 groups of age-matched controls. Results HIV KS participants were younger than cKS (aged 53 vs 75 years). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted, and senescent T-cell frequencies were similar between HIV KS and cKS. Anti–HHV-8 immunoglobulin G levels were higher and circulating HHV-8 DNA lower in HIV KS compared with cKS. Circulating platelet-derived growth factors AA-BB and granulocyte colony-stimulating factors were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients. Conclusions Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti–HHV-8 immunoglobulin G levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART. [ABSTRACT FROM AUTHOR]

Background: Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV‐8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). Objectives: Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. Method: Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. Results: During the follow‐up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. Conclusion: We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus/Acquired immunodeficiency virus (HIV/AIDS) is well known to be a major public health problem globally. On the other hand, HIV/AIDS is associated with various otorhinolaryngological manifestations. On the other hand, there has been a global reduction in the burden of otorhinolaryngological manifestations since the introduction of highly active antiretroviral therapy though there are limited studies on otorhinolaryngological manifestations among HIV/AIDS patients in Tanzania. A hospital based descriptive cross-sectional study was conducted at Ilala District in Dar es Salaam from November 2022 to March 2023 where 380 study participants were recruited using convenience sampling technique. Data was collected using pre-tested semi-structured questionnaires and analysis was done by means of Statistical Package for Social Sciences (SPSS) version 23. Of all the 380 patients recruited in this study, 22 (5.8%) had otorhinolaryngological manifestations. Most of the patients with otorhinolaryngological manifestations were males (6.1%) in the age group 0–9 years (23.1%) followed by those aged 10–19 years (18.8%). The commonest otorhinolaryngological manifestations were allergic rhinitis (22.7%) and otitis externa (22.7%) followed by hearing loss (18.2%), Kaposi's sarcoma (13.7%), tonsillitis (9.1%), chronic suppurative otitis media, (4.5%) sinusitis (4.5%) and adenoid hypertrophy (4.5%). Otitis externa predominated in males (23.1%) while allergic rhinitis predominated in females (33.3%). Similarly, a significant association was found between the occurrence of otorhinolaryngological manifestations with CD4 counts (p-value = 0.001) and viral load (p-value = 0.000). Otorhinolaryngological manifestations among patients living with HIV/AIDS and on highly active antiretroviral therapy were less prevalent. Males outnumbered females in terms of being affected by otorhinolaryngological manifestations. Allergic rhinitis and otitis externa were the commonest otorhinolaryngological manifestations and most of participants with otorhinolaryngological manifestations had viral load of greater than 100 copies and CD4 counts of less than 200cells/mm3. [ABSTRACT FROM AUTHOR]

Background: Renal transplant recipients (RTRs) are prone to skin cancer due to the immunosuppression required to maintain graft function. Existing studies of skin cancer in RTRs focus on patients with Fitzpatrick skin types I‐II, with limited documentation of incidence in skin types III‐VI. This study seeks to better characterize skin cancers in RTRs with skin types III‐VI. Primary aims: Compare the incidence of skin cancer in RTRs of skin types I‐II with skin types III‐VI. Secondary aims: Explore the association between the development of skin cancer and other contributing factors in RTRs of skin types I‐VI. Methods: Retrospective chart review of RTRs at a single institution between January 1, 2000 and December 31, 2022. Patients were followed from the date of transplant to the last clinical follow‐up or death. 777 RTRs were included in the study, including 245 patients with Fitzpatrick skin types I‐II and 532 with skin types III‐VI. A total of 48 patients developed NMSCs, 2 patients developed melanoma, and 3 patients developed Kaposi sarcoma. Results and conclusions: There is a higher incidence of skin cancer in RTRs with Fitzpatrick skin types III‐VI compared to the reported incidence among non‐transplant recipients of the same skin types, but the incidence remains considerably lower compared to RTR of skin types I‐II. [ABSTRACT FROM AUTHOR]

Kaposi’s sarcoma herpesvirus (KSHV) ORF34 plays a significant role as a component of the viral pre-initiation complex (vPIC), which is indispensable for late gene expression across beta- and gammaherpesviruses. Although the key role of ORF34 within the vPIC and its function as a hub protein have been recognized, further clarification regarding its specific contribution to vPIC functionality and interactions with other components is required. This study employed a deep learning algorithm-assisted structural model of ORF34, revealing highly conserved amino acid residues across human beta- and gammaherpesviruses localized in structured domains. Thus, we engineered ORF34 alanine-scanning mutants by substituting conserved residues with alanine. These mutants were evaluated for their ability to interact with other vPIC factors and restore viral production in cells harboring the ORF34-deficient KSHV-BAC. Our experimental results highlight the crucial role of the four cysteine residues conserved in ORF34: a tetrahedral arrangement consisting of a pair of C-Xn-C consensus motifs. This suggests the potential incorporation of metal cations in interacting with ORF24 and ORF66 vPIC components, facilitating late gene transcription, and promoting overall virus production by capturing metal cations. In summary, our findings underline the essential role of conserved cysteines in KSHV ORF34 for effective vPIC assembly and viral replication, thereby enhancing our understanding of the complex interplay between the vPIC components. IMPORTANCE The initiation of late gene transcription is universally conserved across the beta- and gammaherpesvirus families. This process employs a viral pre-initiation complex (vPIC), which is analogous to a cellular PIC. Although KSHV ORF34 is a critical factor for viral replication and is a component of the vPIC, the specifics of vPIC formation and the essential domains crucial for its function remain unclear. Structural predictions suggest that the four conserved cysteines (C170, C175, C256, and C259) form a tetrahedron that coordinates the metal cation. We investigated the role of these conserved amino acids in interactions with other vPIC components, late gene expression, and virus production to demonstrate for the first time that these cysteines are pivotal for such functions. This discovery not only deepens our comprehensive understanding of ORF34 and vPIC dynamics but also lays the groundwork for more detailed studies on herpesvirus replication mechanisms in future research. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is an angio‐proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS‐CoV‐2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non‐latent viral infections. We report a case series of KS characterized by tumor progression after SARS‐CoV‐2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS‐CoV‐2," "HHV‐8," "Kaposi's sarcoma," "IL‐6," and "COVID‐19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID‐19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS‐CoV‐2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS‐CoV‐2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma‐associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV‐1 TAT protein can be essential in developing AIDS‐associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV‐specific TAT profile among PLHIV who developed KS. [ABSTRACT FROM AUTHOR]