Search

The spectrum of HHV-8-associated disorders includes Kaposi's sarcoma, primary effusion lymphoma, multicentric Castleman's disease, and the recently described KSHV inflammatory cytokine syndrome (KICS), a life-threatening disorder complicating HIV infection. There have been no reports in the literature concerning non-immunosuppressed individuals affected with KICS. We report here a KICS-like illness occurring in two elderly Greek men without HIV infection or other recognizable cause of immunosuppression. [ABSTRACT FROM AUTHOR]

This article, published in the Veterinary Record Case Reports, describes a case of cutaneous haemangiosarcoma with ovarian metastases in an aquarium-managed mirror carp. The study highlights the limited scientific literature on neoplasia in common carp and mirror carp, with only a few reported cases of different types of tumors. The case presented in this article is significant because cutaneous haemangiosarcoma has not been previously reported in carp. The study emphasizes the potential for metastasis in fish neoplasia and the importance of local invasion as a determinant feature of malignancy. The authors conclude that further research is needed to understand the behavior and predilections of haemangiosarcoma in carp species. [Extracted from the article]

Background: Multicentric Castleman disease (MCD) is a rare, aggressive lymphoproliferative disorder. Human herpesvirus-8 (HHV-8) has an important role in the pathogenesis of the disease and its association with Kaposi’s sarcoma has been reported, especially in people living with human immunodeficiency virus (HIV). In this report, we present the case of HHV-8 positive MCD accompanied by Kaposi’s sarcoma and multiple myeloma in an HIV-negative patient. Case Report: A 78-year-old man with Kaposi’s sarcoma presented with B symptoms, pancytopenia, lymphadenopathy, and splenomegaly. The bone marrow biopsy demonstrated 70% lambda-restricted monotypic plasma cell infiltration consistent with plasma dyscrasia. Also, the patient was diagnosed with HHV-8 positive MCD as a result of inguinal lymph node excisional biopsy. Treatment was initiated including ganciclovir and methylprednisolone and followed by rituximab. The patient passed away at the 24th hour of rituximab infusion due to shock. Conclusions: MCD and associated malignancies are difficult to treat and have a poor prognosis. More studies and data are needed to manage these patients.

The article explores the expression of programmed cell death proteins in patients with atypical fibroxanthoma and pleomorphic dermal sarcoma, indicating their potential for anti-PD-1/PD-L1 therapy. The study analyzed tissue samples from patients and found higher PD-L1 expression in pleomorphic dermal sarcoma compared to atypical fibroxanthoma. The research suggests that immunotherapeutic interventions may be more relevant for pleomorphic dermal sarcoma due to its higher rate of metastases. The findings also highlight the association of tumor thickness with disease relapse and survival in these types of skin cancers. [Extracted from the article]

Kaposi's sarcoma (KS) is a soft tissue neoplasm of vascular origin arising from cells expressing markers of endothelial smooth muscle and macrophages. Epidemiologically, KS is not considered a common tumor worldwide; however, alongside non-Hodgkin's lymphomas, it is among the most prevalent neoplasms associated with AIDS. Presently, four clinical-epidemiological forms of the disease are recognized: classic, endemic (African), epidemic (AIDS-related), and iatrogenic (post-transplantation). Various forms of KS are characterized by distinct clinical progressions and prognoses, with significant variation in symptoms even within the HIV-infected population. This article presents the case of a young man who reported to a primary healthcare clinic with an uncharacteristic vascular skin lesion on the second toe of his right foot. The atypical clinical picture posed numerous diagnostic challenges, thereby prolonging the time to reach a definitive diagnosis of Kaposi's sarcoma and to initiate appropriate therapeutic measures. [ABSTRACT FROM AUTHOR]

This article, published in the journal Pediatric Dermatology, presents a case study of an 8-year-old boy with a raised lesion on his scalp. The lesion rapidly grew in size over three months and was characterized by an erythematous to yellowish-white, dome-shaped exophytic nodule. The diagnosis was determined to be angiolymphoid hyperplasia with eosinophilia (ALHE) based on histopathological examination. ALHE is a rare vasoproliferative disorder with an unclear etiology, and treatment options include corticosteroids, surgery, cryotherapy, and lasers. The patient in this case study did not experience recurrence after surgical excision. [Extracted from the article]

Abstract Background Clinically, most patients with Kaposi's sarcoma (KS) are male, and several direct and indirect mechanisms may underlie this increased susceptibility in men, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is considered to be the primary etiological agent responsible for KS. Thus, we propose the hypothesis that men are more susceptible to HHV-8 infection, leading to a higher incidence of Kaposi's sarcoma among males. A meta-analysis was conducted to evaluate the association between gender and HHV-8 seropositivity in the general population. Methods A comprehensive literature search was performed using 6 online databases: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, and Wanfang. Studies published before March 15, 2023, were included. Results In all, 33 articles including 41 studies were included in the meta-analysis. In the included adult population. men had a higher risk of HHV-8 infection than did women in adult populations from all over the world (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.15), but no differences were found in child population from all over the world (OR: 0.90, 95% CI: 0.79–1.01). There was a significant difference in HHV-8 seroprevalence between men and women in sub-Saharan Africa (SSA) adult population (OR: 1.15, 95% CI: 1.05–1.26). However, no significant differences were observed in sub-Saharan Africa (SSA) child population (OR: 0.90, 95%CI 0.78–1.03). As for other continents, the results showed no significant difference, such as the Asian population (OR: 1.03, 95%CI: 0.92–1.16). or the European and American populations (OR 1.01, 95%CI 0.87–1.17). Conclusion There was a slight gender disparity for HHV-8 infection in the adult population. Among the adult populations from SSA and globally, men were more likely to be infected with HHV-8 than were women. However, no statistical significance was observed in the child populations from SSA and globally. In the future, the inclusion of more standardized studies may strengthen the results of this study.

Bizunesh Dires Fenta,1 Alazar Berhe Aregawi,2 Teketel Tadesse Geremew,1 Berhanu Kelemework Fenta3 1Department of Pathology, Hawassa University Comprehensive Specialized Hospital, Hawassa, Sidama, Ethiopia; 2Department of Surgery, Hawassa University Comprehensive Specialized Hospital, Hawassa, Sidama, Ethiopia; 3Department of Internal Medicine, Yanet Internal Medicine Specialized Center, Hawassa, Sidama, EthiopiaCorrespondence: Alazar Berhe Aregawi, Tel +251911914624, Email alazarberhe@hu.edu.etAbstract: One kind of angioproliferative disorder is Kaposi’s sarcoma (KS). Growth of spindle-shaped cells, edema, inflammation, and neoangiogenesis are its defining features. Because it lacks the typical indicators of malignancy, it is classified as an intermediate neoplasm. People who are immunocompromised, receiving organ transplants, or receiving antiretroviral therapy are linked to KS. Although lymph node involvement by KS is extremely uncommon, when it does occur, it usually manifests as either the epidemic form in (Human Immuno-deficiency) HIV-positive patients or the endemic form in Africans. There are four primary clinical manifestations of KS that have been documented: endemic, epidemic, iatrogenic, and classic. The diagnosis of KS is made by history, physical examination, and tissue biopsy. When treating localized disease, highly active antiretroviral therapy (HAART) may be sufficient to either improve or completely eradicate the illness. Nonetheless, chemotherapy and HAART would be necessary in the case of widespread illness. Here, we present the case of a 28-year-old female patient who is HIV positive and has a viral load that is not detected. She presented with generalized lymphadenopathy of 8 months duration. She had no cutaneous manifestations. The lymphadenopathy involved the tonsils, axilla, inguinal, and an unusual site, intraparotid on both sides. After a pathologic examination of the lymph nodes, she was found to have epidemic-type KS and was treated with HAART and chemotherapy. In our nation, we are not aware of any published case reports pertaining to a case like this. The purpose of this case report is to raise physicians’ awareness of this uncommon ailment and to encourage them to suspect KS when HIV patients exhibit generalized lymphadenopathy. The early initiation of systemic treatment is lifesaving for these patients.Keywords: Kaposi’s sarcoma, KS, Human immune-deficiency Virus, HIV, human herpes virus-8, Acquired Immuno-deficiency Syndrome, AIDS, generalized lymphadenopathy

Background. The incidence of malignancy is heightened in individuals infected with Human Immunodeficiency Virus (HIV). Despite a decrease in the incidence of HIV infection resulting from antiretroviral therapy (ART), the prevalence of HIV-associated malignancies remains substantial. Objective. Our objective was to examine the types of cancer that initially manifest in individuals infected with HIV or emerge during their subsequent observation period. Material and method. The study conducted a retrospective analysis of demographic characteristics, malignancy types, presenting symptoms, mode of transmission, HIV-RNA levels, and CD4/CD8 ratios in individuals living with HIV who developed malignancies and were under follow-up at the Infectious Diseases Polyclinic between October 2018 and December 2022. Results. Out of the 465 patients who were monitored during the study, 27 individuals (5.8%) were diagnosed with various malignancies. Among these patients, 22 (81%) were men and 5 (19%) were women. The average age of the patients ranged from 45.87 to 9.12 years. Among the patients, 17 (63%) were married and 10 (17%) were single. In terms of education, 16 patients (59.3%) had completed primary school, 7 patients (25.9%) were university graduates, and 4 patients (14.8%) had completed high school. The mode of HIV transmission in all patients was through sexual intercourse. The reasons for testing varied, with 8 patients (29.7%) being tested due to fever, 6 patients (22.2%) before undergoing surgery, 3 patients (11.1%) due to weight loss, and 2 patients (7.4%) tested for reasons such as job application, diarrhea, pre-blood donation, lymphadenomegaly, and dysphagia. The most common types of malignancies observed in the patients were non-Hodgkin’s lymphoma (NHL) with 11 cases (40.7%), followed by Kaposi’s sarcoma (KS) with 5 cases (18.5%), and cervical carcinoma with 3 cases (11.1%). Conclusion. The incidence of cancer is higher among individuals with HIV. There is a need to enhance the awareness among both healthcare providers who specialize in HIV care and those who do not.

Introduction: Since the introduction of Highly Active Anti-Retroviral Therapy (HAART), there has been a significant increase in the survival of HIV-infected patients. Consequently, there has been increased attention on the potential neoplastic pathologies, such as Kaposi’s sarcoma, associated with AIDS in these individuals. Case Report: In this case report we present, for the first time, a patient affected by Kaposi's sarcoma of the palatine tonsil with a concomitant syphilis infection. The patient underwent enlarged tonsillectomy and continued antiretroviral therapy. There were no signs of disease recurrence at a 12-month follow-up. Conclusions: Despite the rarity of tonsillar localization of Kaposi's sarcoma, it should be suspected in the presence of an HIV-infected patient. Tonsillectomy effectively controls local disease, but comprehensive patient management requires a multidisciplinary team of healthcare professionals, including infectious disease specialists, pathologists, and oncologists who work together to provide high-quality and coordinated care.

Chun-Shuang Guan,1,* Jing Yu,2,* Yan-Ni Du,1,* Xin-Gang Zhou,3 Zi-Xin Zhang,1 Hui Chen,1 Yu-Xue Xing,1 Ru-Ming Xie,1 Zhi-Bin Lv1 1Department of Radiology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Ultrasonography, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ru-Ming Xie; Zhi-Bin Lv, Tel +8613911320739 ; +8613683151127, Email mingrux1@163.com; xiaochun324@126.comPurpose: To retrospectively analyse the different imaging manifestations of acquired immunodeficiency syndrome-associated hepatic Kaposi’s sarcoma (AIDS-HKS) on CT, MRI, and Ultrasound.Patients and Methods: Eight patients were enrolled in the study. Laboratory tests of liver function were performed. The CT, MRI, and Ultrasound manifestations were reviewed by two radiologists and two sonographers, respectively. The distribution and imaging signs of AIDS-HKS were evaluated.Results: AIDS-HKS patients commonly presented multiple lesions, mainly distributed around the portal vein on CT, MRI, and Ultrasound. AIDS-HKS presented as ring enhancement in the arterial phase on contrast-enhanced CT and MRI scanning, and nodules gradually strengthen in the portal venous phase and the delayed phase. AIDS-HKS presented as intrahepatic bile duct dilatation and bile duct wall thickening around the lesion. Five patients (62.5%, 5/8) were followed up. After chemotherapy, the lesions were completely relieved (60.0%), or decreased (40.0%).Conclusion: AIDS-HKS presented as multiple nodular lesions with different imaging features. The combination of different imaging methods was helpful for the imaging diagnosis of AIDS-HKS.Keywords: Kaposi’s sarcoma, liver, diagnostic imaging, magnetic resonance imaging, tomography, spiral computed, ultrasonography

BackgroundFor people with advanced-stage Kaposi's sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya.MethodsThis is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016-2020) to the period after (2021-2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy.DiscussionThis study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.

Kaposi sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern United States. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for KS-associated herpesvirus (KSHV) IgG. Seroprevalence, seroconversion between time points, and demographic and clinical correlates were measured. KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years. Furthermore, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS diagnosis and outcomes. [ABSTRACT FROM AUTHOR]

During viral infection, the innate immune system utilizes a variety of specific intracellular sensors to detect virus-derived nucleic acids and activate a series of cellular signaling cascades that produce type I IFNs and proinflammatory cytokines and chemokines. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus that has been associated with a variety of human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Infection with KSHV activates various DNA sensors, including cGAS, STING, IFI16, and DExD/H-box helicases. Activation of these DNA sensors induces the innate immune response to antagonize the virus. To counteract this, KSHV has developed countless strategies to evade or inhibit DNA sensing and facilitate its own infection. This review summarizes the major DNA-triggered sensing signaling pathways and details the current knowledge of DNA-sensing mechanisms involved in KSHV infection, as well as how KSHV evades antiviral signaling pathways to successfully establish latent infection and undergo lytic reactivation. [ABSTRACT FROM AUTHOR]

Blockade of the co-inhibitory receptor PD-1 enhances antitumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here, we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti–PD-1 therapy for Kaposi sarcoma in people with HIV well-controlled on antiretroviral therapy. Less than a week after receiving the first dose of anti–PD-1 antibody (pembrolizumab), he presented with severe abdominal pain associated with sudden exacerbations of preexisting cytomegalovirus (CMV) enteritis and nontuberculous mycobacterial mesenteric lymphadenitis. Plasma biomarkers of gastrointestinal tract damage were highly elevated compared with healthy controls, consistent with HIV-associated loss of gut epithelial barrier integrity. Moreover, CMV-specific CD8 T cells expressed high levels of PD-1, and 7 days following PD-1 blockade, there was an increase in the frequency of activated CD38+ Ki67+ CMV-specific CD8 T cells. This case highlights the potential for PD-1 blockade to drive rapid exacerbations of inflammatory symptoms when administered to individuals harboring multiple unresolved infections. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma (KS) arises in the context of 4 epidemiologic-clinical settings: Classic, endemic, epidemic, and iatrogenic; the most serious types are endemic and epidemic, and visceral involvement occurs mostly in the latter. Several morphological variants of KS have been described, of which the anaplastic one is highly aggressive. We report the case of an anaplastic KS arising from the ascending colon in a 32-year-old human immunodeficiency virus (HIV)-positive male patient with a 6-year history of multiple mucocutaneous KS. Anaplastic KS is most frequent in endemic and classic settings; there are ten cases of anaplastic KS reported in HIV-positive male patients. There is now strong evidence that KS is a clonal neoplasm characterized by chromosomal instability at the molecular level. According to the morphological spectrum and contemporary hypotheses of oncogenesis, conventional KS should be considered an incipient endothelial neoplasia, multiple or single, and anaplastic KS, the fully developed stage of the malignant neoplasm. [ABSTRACT FROM AUTHOR]

This article discusses two cases of Kaposi sarcoma (KS) in Russian patients who had undergone kidney transplantation and were receiving immunosuppressive therapy. KS is a vascular disease that affects various parts of the body, including the skin. The article highlights the importance of human herpesvirus-8 (HHV-8) as a potential trigger for KS, particularly in transplant recipients. The patients presented with characteristic skin lesions and were found to be HHV-8 positive. The article suggests that testing donors and recipients for HHV-8 before transplantation could help predict the risk and prognosis of KS. [Extracted from the article]

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)‐infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV‐infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV‐induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal‐to‐endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV‐induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment. [ABSTRACT FROM AUTHOR]

Human Herpesvirus 8 (HHV‐8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV‐8 in an Irish population. This retrospective study included 30 patients who had HHV‐8 DNA detected in plasma. Nested end‐point PCR was used to characterise four regions of the HHV‐8 genome, K1, T0.7 (K12), ORF 75, and K15. Sequencing data were obtained for 23 specimens from 19 patients. Phylogenetic analysis of ORF K1 demonstrated that subtypes A, B, C and F were present in 37%, 11%, 47% and 5%, respectively. For T0.7 and ORF 75, sequencing data were obtained for 12 patients. For T0.7, subtypes A/C, J, B, R and Q were present in 58%, 17%, 8%, 8%, and 8%, respectively. For ORF 75, subtypes A, B, C and D were present in 58%, 8%, 25%, and 8%, respectively. K15 sequences were determined for 13 patients. 69% had the P allele and 31% had the M allele. The data generated by this study demonstrate that a broad variety of HHV‐8 subtypes are represented in patients exhibiting HHV‐8‐related disease in Ireland, a low prevalence country. The predominance of C and A K1 subtypes was as expected for a Western European population. The 31% prevalence for K15 subtype M was higher than expected for a Western European population. This may represent the changing and evolving epidemiology in Ireland due to altered migration patterns. [ABSTRACT FROM AUTHOR]

Background: Clinically, most patients with Kaposi's sarcoma (KS) are male, and several direct and indirect mechanisms may underlie this increased susceptibility in men, Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is considered to be the primary etiological agent responsible for KS. Thus, we propose the hypothesis that men are more susceptible to HHV-8 infection, leading to a higher incidence of Kaposi's sarcoma among males. A meta-analysis was conducted to evaluate the association between gender and HHV-8 seropositivity in the general population. Methods: A comprehensive literature search was performed using 6 online databases: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, and Wanfang. Studies published before March 15, 2023, were included. Results: In all, 33 articles including 41 studies were included in the meta-analysis. In the included adult population. men had a higher risk of HHV-8 infection than did women in adult populations from all over the world (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.15), but no differences were found in child population from all over the world (OR: 0.90, 95% CI: 0.79–1.01). There was a significant difference in HHV-8 seroprevalence between men and women in sub-Saharan Africa (SSA) adult population (OR: 1.15, 95% CI: 1.05–1.26). However, no significant differences were observed in sub-Saharan Africa (SSA) child population (OR: 0.90, 95%CI 0.78–1.03). As for other continents, the results showed no significant difference, such as the Asian population (OR: 1.03, 95%CI: 0.92–1.16). or the European and American populations (OR 1.01, 95%CI 0.87–1.17). Conclusion: There was a slight gender disparity for HHV-8 infection in the adult population. Among the adult populations from SSA and globally, men were more likely to be infected with HHV-8 than were women. However, no statistical significance was observed in the child populations from SSA and globally. In the future, the inclusion of more standardized studies may strengthen the results of this study. [ABSTRACT FROM AUTHOR]

Chemokines play a key role in cancer processes, with CXCL1 being a well-studied example. Due to the lack of a complete summary of CXCL1's role in cancer in the literature, in this study, we examine the significance of CXCL1 in various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi's sarcoma, lung, osteosarcoma, renal, and skin cancers (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma), along with thyroid cancer. We focus on understanding how CXCL1 is involved in the cancer processes of these specific types of tumors. We look at how CXCL1 affects cancer cells, including their proliferation, migration, EMT, and metastasis. We also explore how CXCL1 influences other cells connected to tumors, like promoting angiogenesis, recruiting neutrophils, and affecting immune cell functions. Additionally, we discuss the clinical aspects by exploring how CXCL1 levels relate to cancer staging, lymph node metastasis, patient outcomes, chemoresistance, and radioresistance. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD) are both linked to human herpesvirus-8 (HHV-8) infection which most commonly affects people living with human immunodeficiency virus (HIV). Herein, we describe the case of a 57-year-old patient who has been admitted for fever, night sweats, weight loss, and diffuse lymphadenopathy with abdominal pain. HIV status was confirmed by a positive Western blot test. His initial CD4 cell count was equal to 270 cells/µL. A histological study of a peripheral lymph node concluded that KS is associated with MCD. These two conditions found in the same patient highlight the malignant potential of HHV-8, particularly in the case of HIV-induced immunodeficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: Electrochemotherapy (ECT) should be considered a valid therapeutical strategy for the local control of widespread and advanced CKS cutaneous and subcutaneous lesions. The aim of our study is not only to validate and confirm that ECT represents the best therapeutical choice in terms of the risk–benefit ratio for the treatment of cutaneous and subcutaneous lesions in non-advanced forms of Kaposi's sarcoma, but also to demonstrate the valid use of ECT for the local control of locally advanced classic Kaposi's sarcoma (CKS). Among 19 patients treated, acceptable results have also been obtained in those patients with widespread CKS lesions due to the silent course of the KS classic variant and the excellent impact of the disease on quality of life. Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as a medical procedure for skin neoplasms' treatment, especially for classic Kaposi's sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and the local control of CKS disease. The primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions' treatment. In total, 19 CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt; meanwhile, 3 and 4 out of 19 patients obtained a partial response (PR), so they underwent a second and third ECT treatment, respectively. Clinical response was evaluated during the entire timeframe of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. The control of CKS skin lesions still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors' recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi's sarcoma locally advanced lesions. [ABSTRACT FROM AUTHOR]

Human herpesvirus 8 (HHV8)-associated diseases include Kaposi sarcoma (KS), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD), Kaposi sarcoma inflammatory cytokine syndrome (KICS), HHV8-positive diffuse large B-cell lymphoma (HHV8+ DLBCL), primary effusion lymphoma (PEL), and extra-cavitary PEL (ECPEL). We report the case of a human immunodeficiency virus (HIV)-negative male treated for cutaneous KS, who developed generalized lymphadenopathy, hepatosplenomegaly, pleural and abdominal effusions, renal insufficiency, and pancytopenia. The excised lymph node showed features of concomitant involvement by micro-KS and MCD, with aggregates of HHV8+, Epstein Barr virus (EBV)-negative, IgM+, and lambda+ plasmablasts reminiscent of microlymphoma. Molecular investigations revealed a somatically hypermutated (SHM) monoclonal rearrangement of the immunoglobulin heavy chain (IGH), accounting for 4% of the B-cell population of the lymph node. Mutational analyses identified a pathogenic variant of KMT2D and variants of unknown significance in KMT2D, FOXO1, ARID1A, and KMT2A. The patient died shortly after surgery. The histological features (HHV8+, EBV−, IgM+, Lambda+, MCD+), integrated with the molecular findings (monoclonal IGH, SHM+, KMT2D mutated), supported the diagnosis of a monoclonal HHV8+ microlymphoma, with features intermediate between an incipient HHV8+ DLBCL and an EBV-negative ECPEL highlighting the challenges in the accurate classification of HHV8-driven lymphoid proliferations. [ABSTRACT FROM AUTHOR]

Introduction: Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with HIV/AIDS (PWHA). PWHA with advanced immunosuppression who initiate antiretroviral therapy are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS). Case Presentation: This report covers the case of a 25-year-old male with AIDS-related KS who relapsed after Liposomal Doxorubicin, but recovered well after administration of nab-paclitaxel (Nab-PTX). Conclusion: This is a rare case in choosing Nab-PTX to treat relapsed AIDS-KS and get good feedback. We report the case to provide a possible solution to treat AIDS-KS. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel is a chemotherapeutic agent commonly used for ovarian, lung, breast carcinoma, and Kaposi's sarcoma. Its common side effects include hypersensitivity reaction, bone marrow suppression, and peripheral neuropathy. However, a rare and life-threatening side effect is paclitaxel-induced myocardial infarction. Case presentation: A 71-year-old man with type 2 diabetes mellitus, hypertension, heavy smoking history, previous coronary artery disease with percutaneous coronary intervention (PCI) in left anterior descending artery (LAD), and non-small lung cancer presented with non-ST elevation myocardial infarction during infusion of paclitaxel infusion. Coronary angiogram showed de novo three vessel disease with 70% stenosis in ostial to distal left main artery (LM) and 80% in-stent re-stenosis in proximal to mid left anterior descending artery. Conclusions: Physicians should be keeping this in mind when dealing with patients on paclitaxel, especially if they have previous risk factors for coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) aspartyl protease. Previous studies demonstrated that this drug could also inhibit Kaposi's sarcoma-associated herpesvirus (KSHV) production. Our laboratory demonstrated nelfinavir can effectively inhibit herpes simplex virus type 1 (HSV-1) replication. For HSV-1 we were able to determine that virus capsids were assembled and exited the nucleus but did not mature in the cytoplasm indicating the drug inhibited secondary envelopment of virions. Methods: For KSHV, we recently derived a tractable cell culture system that allowed us to analyze the virus replication cycle in greater detail. We used this system to further define the stage at which nelfinavir inhibits KSHV replication. Results: We discovered that nelfinavir inhibits KSHV extracellular virus production. This was seen when the drug was incubated with the cells for 3 days and when we pulsed the cells with the drug for 1–5 min. When KSHV infected cells exposed to the drug were examined using ultrastructural methods there was an absence of mature capsids in the nucleus indicating a defect in capsid assembly. Because nelfinavir influences the integrated stress response (ISR), we examined the expression of viral proteins in the presence of the drug. We observed that the expression of many were significantly changed in the presence of drug. The accumulation of the capsid triplex protein, ORF26, was markedly reduced. This is an essential protein required for herpesvirus capsid assembly. Conclusions: Our studies confirm that nelfinavir inhibits KSHV virion production by disrupting virus assembly and maturation. This is likely because of the effect of nelfinavir on the ISR and thus protein synthesis and accumulation of the essential triplex capsid protein, ORF26. Of interest is that inhibition requires only a short exposure to drug. The source of infectious virus in saliva has not been defined in detail but may well be lymphocytes or other cells in the oral mucosa. Thus, it might be that a "swish and spit" exposure rather than systemic administration would prevent virion production. [ABSTRACT FROM AUTHOR]

Background Males have 2–3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults. Methods Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test. Results Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P  <  .0001), stomach (1.51 vs 2.09; P  =  .002), colorectum (0.98 vs 1.43; P  <  .0001), liver (2.39 vs 3.44; P  =  .002), kidney (1.67 vs 2.24; P  <  .0001), bladder (2.02 vs 4.19; P  <  .0001), Kaposi sarcoma (1.79 vs 3.26; P  =  .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P  <  .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites. Conclusions Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Since the introduction of Highly Active Anti-Retroviral Therapy (HAART), there has been a significant increase in the survival of HIV-infected patients. Consequently, there has been increased attention on the potential neoplastic pathologies, such as Kaposi’s sarcoma, associated with AIDS in these individuals. Case Report: In this case report we present, for the first time, a patient affected by Kaposi's sarcoma of the palatine tonsil with a concomitant syphilis infection. The patient underwent enlarged tonsillectomy and continued antiretroviral therapy. There were no signs of disease recurrence at a 12-month follow-up. Conclusions: Despite the rarity of tonsillar localization of Kaposi's sarcoma, it should be suspected in the presence of an HIV-infected patient. Tonsillectomy effectively controls local disease, but comprehensive patient management requires a multidisciplinary team of healthcare professionals, including infectious disease specialists, pathologists, and oncologists who work together to provide high-quality and coordinated care. [ABSTRACT FROM AUTHOR]

Castleman's disease (CD), known as angiofollicular lymph node hyperplasia, is an uncommon condition. The two most common histological subtypes are hyaline vascular and plasma cell. We performed a retrospective analysis to define the clinic-pathological features and survival of CD, which is quite rare focusing on the particularities of our series with a review of the recent literature. This is a retrospective study conducted in the department of internal medicine of Hedi Chaker hospital in Sfax, Tunisia over 25 years. The disease was histologically confirmed in all patients. For each file, we collected a set of data by filling in a pre-designed form. 18 patients were included. There were 8 men and 10 women with a mean age of 42.8 years. CD was monocentric in 5 cases (28%) and multicentric in 13 cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13 patients, including general condition (4.4%), fever (16.6%), serositis (27.7%), and skin involvement (33.3%). A biological inflammatory syndrome accompanied the clinical picture in 66% of patients. Abnormalities in the blood count were found in 12 cases (66%), with anemia in 11 cases, thrombocytosis in 3 cases, and hypereosinophilia in 3 cases. Cutaneous Kaposi's sarcoma was associated with Castleman's disease in 2 cases, Hodgkin's lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1 case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren's syndrome in 2 cases and rheumatoid arthritis in 1 case. HHV8 serology was positive in 1 case with a multicentric plasma cell form. Histologically, the plasma cell form represented 50% of cases, hyaline-vascular (39% of cases), and mixed (11% of cases). Therapeutically, high-dose corticosteroid therapy was initiated in 13 cases. As a second-line treatment, MOPP chemotherapy was used in 1 case due to transformation into Hodgkin's lymphoma, and biotherapy (rituximab) was used in 2 cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2 patients with monocentric CD. : Castleman's disease (CD) is a non-malignant lymphoproliferation of localized or multicentric form with a wide and heterogeneous clinical spectrum. Diagnosis can be difficult due to the lack of clinical and radiological specificity. Management depends on the clinical form involving surgical and/or medical management. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is an uncommon angioproliferative tumour. In its classic form, it rarely affects the head and neck. The etiologic agent in KS is Human Herpesvirus type-8 (HHV-8) infection. Populations in which KS occurs in the setting of immunocompetence tend to have high rates of seropositivity for HHV-8, including Mediterranean and Jewish people. Descriptions of KS in immunocompetent Polynesian individuals are almost non-existent. A reason for this may be the relative inaccessibility, both geographically and culturally, of indigenous peoples living in the Oceanic area. High rates of HHV-8 seropositivity have recently been reported in indigenous Melanesian populations of Vanuatu, New Caledonia and Papua New Guinea, a region neighbouring Polynesia. This paper is the first to describe classic KS isolated to the oral cavity in an immunocompetent patient of Polynesian ancestry and highlights the need for further research to clarify the risk of KS emerging in this region.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as “bubbling” in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

Kaposi’s sarcoma is an uncommon malignant vascular neoplasm linked to human herpesvirus type 8 (HHV-8); it is a tumor characterized by proliferation of HHV-8-associated spindle cells and abnormal neo-vasculature. Although Kaposi’s sarcoma has been described in immunocompetent subjects, strong inter-relationships with host immunity lead to higher prevalence in people living with human immunodeficiency virus (HIV). HIV infection has been historically associated with malignancies, such as Kaposi’s sarcoma. Usually, it causes abnormalities that develop in tissues below the skin surface anywhere on the body or in mucous membranes of the mouth. Some authors have observed that malignancy is becoming a major cause of death among HIV-infected individuals in industrialized nations. In non-industrialized countries, profound weaknesses have been demonstrated in the diagnostic muscle of infectious diseases in general, with viral diseases being no exception. Treatment may consist of surgery, chemotherapy, or a combination of these treatment techniques. Combination of two or more of these treatment methods has become an important approach for increasing patient’s chance of cure and prolonging survival. There are four clinical presentations: classic, endemic, associated with iatrogenic immunosuppression, and associated with acquired immunodeficiency syndrome. This article presented a clinical case of an HIV-seropositive patient affected by disseminated angiomatous lesions, diagnosis, therapeutic options, and evolution.

Objective: Kaposi’s sarcoma (KS) is a vascular proliferation associated with Human Herpes Virus 8. Typical histopathological findings of KS are characterized by vascular proliferation, inflammatory cell infiltration, extravasated erythrocytes and spindle cell proliferation, although it varies according to the stage. In this study, the clinical-histopathological features of patients with KS were examined. The value of histopathological parameters in the diagnosis was investigated. Methods: Patients with KS diagnosed in University of Health Sciences Turkey, Samsun Training and Research Hospital Medical Pathology Department between 2016-2020 were retrospectively scanned. Clinical and tumor features and histopathological changes in the surrounding tissue were evaluated. Results: The most common histopathological features belonging to tumor were extravasated erythrocytes, spindle cell changes, fascicle formation, slit-like space; the most common epidermal features were hyperkeratosis and acanthosis; the most common peritumoral features were the presence of large vessels and ectatic vessels in the periphery. There was a significant relationship between the promontory sign and the lymphangioma-like area and ulcer. Also there was a significant relationship between nuclear atypia and lymphangioma-like area. Conclusion: While most of the histopathological features are characteristic for KS, none of them alone is specific. They should be evaluated together with all structural, tumoral and peritumoral features during the diagnostic approach.

Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV‐8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV‐8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first‐ever instance of HHV‐8 encephalitis in a SOT recipient. Our case highlights the association of HHV‐8‐related diseases, such as post‐transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV‐8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV‐8‐related diseases in SOT recipients, as they are at risk of developing such infections. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of disseminated Kaposi sarcoma (KS) in a kidney transplant recipient without primary cutaneous involvement. The patient, a 69-year-old male, had a history of end-stage renal disease and had undergone a kidney transplant. The KS was complicated by KSHV-inflammatory cytokine syndrome (KICS), which presented as multi-system inflammation. The patient's case was atypical because it occurred in the United States without known geographic or sexual risk factors. The article provides information on the prevalence, diagnosis, and treatment of KS in transplant recipients. [Extracted from the article]

This article discusses the risk of developing Kaposi sarcoma (KS) as a second primary cancer in individuals who have already had a malignancy. The study analyzed data from over 6 million individuals and found that males, particularly those under 40, had the highest risk of developing KS within a year of their initial cancer. Patients who received chemotherapy had the highest increased risk of KS compared to other treatments. The study also found that patients of all genders had an increased risk of developing cancers of the anorectum, lymphoma, and leukemia. The study suggests that immune dysregulation and viral infections may contribute to the development of KS. Providers are advised to be vigilant for KS in male patients who have had certain types of cancers. [Extracted from the article]

This document is an interview with Professor Michel Janier, a prominent figure in the field of dermatology and venereology. Professor Janier discusses his background, education, and professional achievements, including his role in keeping venereology within the field of dermatology. He also mentions his disappointment that young doctors are not familiar with the pioneers of dermatology. Professor Janier shares his favorite writer, composer, and painter, and expresses his belief that venereology needs dermatology experts. He predicts that the greatest problem in dermatology in the next 10 years will be the overwhelming importance of aesthetics, and he believes that artificial intelligence will be the next breakthrough in the field. [Extracted from the article]

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

Protein-level immunodominance patterns against Kaposi sarcoma-associated herpesvirus (KSHV), the aetiologic agent of Kaposi sarcoma (KS), have been revealed from serological probing of whole protein arrays, however, the epitopes that underlie these patterns have not been defined. We recently demonstrated the utility of phage display in high-resolution linear epitope mapping of the KSHV latency-associated nuclear antigen (LANA/ORF73). Here, a VirScan phage immunoprecipitation and sequencing approach, employing a library of 1,988 KSHV proteome-derived peptides, was used to quantify the breadth and magnitude of responses of 59 sub-Saharan African KS patients and 22 KSHV-infected asymptomatic individuals (ASY), and ultimately to support an application of machine-learning-based predictive modeling using the peptide-level responses. Comparing anti-KSHV antibody repertoire revealed that magnitude, not breadth, increased in KS. The most targeted epitopes in both KS and ASY were in the immunodominant proteins, notably, K8.129−56 and ORF65140-168, in addition to LANA. Finally, using unbiased machine-learning-based predictive models, reactivity to a subset of 25 discriminative peptides was demonstrated to successfully classify KS patients from asymptomatic individuals. Our study provides the highest resolution mapping of antigenicity across the entire KSHV proteome to date, which is vital to discern mechanisms of viral pathogenesis, to define prognostic biomarkers, and to design effective vaccine and therapeutic strategies. Future studies will investigate the diagnostic, prognostic, and therapeutic potential of the 25 discriminative peptides. Author summary: Kaposi sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of sub-Saharan African endemic Kaposi sarcoma (EnKS) and HIV-associated epidemic KS (EpKS). The humoral immune response against KSHV has been studied using infected cell immunofluorescence assays and immunoassays against recombinant proteins. The latency-associated nuclear antigen (LANA) has been established as the most antigenic KSHV protein, and seroreactivity to LANA and the glycoprotein K8.1 are common determinants of KSHV infection. While protein-level antigenicity of a near-complete KSHV proteome has been reported, the epitopes within those proteins have not yet been defined. We have recently demonstrated the utility of phage display in facilitating the first high-resolution epitope mapping of the highly antigenic LANA protein and now apply that same approach to the entire KSHV proteome. Our study presents the most comprehensive and highest-resolution antibody profiling of the KSHV peptidome to date and provides a direct comparison of responses in KS patients and asymptomatic KSHV-seropositive individuals with and without HIV-1 co-infection. The antibody repertoire and epitopes defined here are valuable to furthering the discovery of prognostic biomarkers as well as designing effective preventatives and therapeutics. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood. Carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) is a key enzyme of the de novo pyrimidine synthesis, and was recently identified to deamidate the NF-κB subunit RelA to promote aerobic glycolysis and cell proliferation. Here we report that KSHV infection exploits CAD for nucleotide synthesis and glycolysis. Mechanistically, KSHV vCyclin binds to and hijacks cyclin-dependent kinase CDK6 to phosphorylate Ser-1900 on CAD, thereby activating CAD-mediated pyrimidine synthesis and RelA-deamidation-mediated glycolytic reprogramming. Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases. The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is known to reprogram cellular metabolism. Here, Wan et al show that viral Cyclin exploits host nucleotide synthesis and glycolysis to support KSHV pathogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi's sarcoma (KS) is a low-grade, vascular tumor associated with human herpesvirus 8 (HHV8) infection. There are four widely recognized types of KS including classic, endemic, iatrogenic, and epidemic forms. Although in most cases, KS is an indolent disease limited to the skin, it may have a more aggressive behavior resulting in locally aggressive disease and/or involving the mucosae or visceral organs, especially in immunosuppressed patients. The main risk factors are HHV-8 infection and immunosuppression status. The treatment is very heterogenous, because there is still no unified strategy for the treatment of KS. The aim of this study is to describe the demographic and clinical features, treatment outcomes, and prognosis of a cohort of patients affected by KS treated at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV) between 1993 and 2022. Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical–epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan–Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up. [ABSTRACT FROM AUTHOR]

Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV− patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status. Experimental regiment includes 4 weeks of valganciclovir before starting the antiretroviral therapy in DKS/HIV patients. Experimental regime (ER) induces a homogeneous distribution of activated CD4+ T cells and modulates efficiently the tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) levels. ER can provide a clinical benefit because an exacerbated inflammatory process could be avoided. Graphical Abstract [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) is an AIDS-defining illness caused by Kaposi's sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients' blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients' blood (median: 280.5/106 cells (IQR: 69.7–1727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9/106 cells, IQR: 70.5–11,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28–24.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T1 stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes. [ABSTRACT FROM AUTHOR]

Aims: Follicular helper T‐cell (TFH) lymphoma of the angioimmunoblastic‐type (AITL), one of the most prevalent T‐cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein–Barr virus‐positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Methods and results: Three male patients aged 49–76 years, HIV‐negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+, HHV8+ spindle cells. High‐throughput sequencing showed AITL‐associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Conclusion: Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open. [ABSTRACT FROM AUTHOR]

Dermatofibroma is a commonly occurring cutaneous entity usually centered within the skin's dermis. Dermatofibromas are referred to as benign fibrous histiocytomas of the skin, superficial/cutaneous benign fibrous histiocytomas, or common fibrous histiocytoma. These mesenchymal cell lesions of the dermis clinically are firm subcutaneous nodules that occur on the extremities in the vast majority of cases and may or may not be associated with overlying skin changes. A 20 years old male presented to ENT OPD, at a private hospital, with complaints of a huge mass over right side of face since 15 years, which was slowly growing and not associated with pain. On clinical examination, hard, non tender, lobulated cauliflower like mass located over right side of face extending from right side temporal region to upper border of mandible from superior to inferior. From anterior to posterior it was extending from lateral 1/3rd of forehead and covering lateral canthus of right eye upto right side tragus. We have taken incisional biopsy which was suggestive of dermatofibroma. Then surgery was performed with patient's consent. Excision with 1 cm free margin was done. Raw area was covered with full thickness skin grafting and advancement flap. We found no recurrence till date. Dermatofibroma in the head and neck region is less common and often present a difficult differential diagnosis like Dermatofibrosarcoma protuberans, Kaposi Sarcoma, Basal cell carcinomas. The aim of case report is to represent case of dermatofibroma of epitheloid variety which is unusual in size. [ABSTRACT FROM AUTHOR]

Simple Summary: Following infection with HIV, individuals are immunocompromised. Their weakened immune system puts them at a higher risk of certain cancers like Kaposi sarcoma and lymphoma. Even with antiretroviral therapy for HIV infection, these cancers remain common in developing countries, while in developed countries, there is a decline in some cancers but an increase in deaths from others. This review explores why these cancers happen in people with HIV and finds that the current treatment is not enough to prevent them. Understanding these reasons is crucial to improving the diagnosis and treatment of both HIV and its associated cancers, highlighting the need for more research to tackle this ongoing health issue. The immune deficiency associated with human immunodeficiency virus (HIV) infection causes a distinct increased risk of developing certain cancer types. Kaposi sarcoma (KS), invasive cervical cancer and non-Hodgkin's lymphoma (NHL) are the prominent malignancies that manifest as a result of opportunistic viral infections in patients with advanced HIV infection. Despite the implementation of antiretroviral therapy (ART), the prevalence of these acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) remains high in developing countries. In contrast, developed countries have experienced a steady decline in the occurrence of these cancer types. However, there has been an increased mortality rate attributed to non-ADMs. Here, we provide a review of the molecular mechanisms that are responsible for the development of ADMs and non-ADMs which occur in HIV-infected individuals. It is evident that ART alone is not sufficient to fully mitigate the potential for ADMs and non-ADMs in HIV-infected individuals. To enhance the diagnosis and treatment of both HIV and malignancies, a thorough comprehension of the mechanisms driving the development of such cancers is imperative. [ABSTRACT FROM AUTHOR]

Objective: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy. Method: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles. Results: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC. Conclusion: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort. [ABSTRACT FROM AUTHOR]

Intussusceptive angiogenesis (IA) and intussusceptive lymphangiogenesis (IL) play a key role in the growth and morphogenesis of vessels. However, there are very few studies in this regard in vessel tumors (VTs). Our objective is to assess the presence, characteristics, and possible mechanisms of the formation of intussusceptive structures in a broad spectrum of VTs. For this purpose, examples of benign and malignant blood and lymphatic VTs were studied via conventional procedures, semithin sections, and immunochemistry and immunofluorescence microscopy. The results demonstrated intussusceptive structures (pillars, meshes, and folds) in benign (lobular capillary hemangioma or pyogenic granuloma, intravascular papillary endothelial hyperplasia or Masson tumor, sinusoidal hemangioma, cavernous hemangioma, glomeruloid hemangioma, angiolipoma, and lymphangiomas), low-grade malignancy (retiform hemangioendothelioma and Dabska tumor), and malignant (angiosarcoma and Kaposi sarcoma) VTs. Intussusceptive structures showed an endothelial cover and a core formed of connective tissue components and presented findings suggesting an origin through vessel loops, endothelialized thrombus, interendothelial bridges, and/or splitting and fusion, and conditioned VT morphology. In conclusion, the findings support the participation of IA and IL, in association with sprouting angiogenesis, in VTs, and therefore in their growth and morphogenesis, which is of pathophysiological interest and lays the groundwork for in-depth molecular studies with therapeutic purposes. [ABSTRACT FROM AUTHOR]