Cases Of Kaposi's Sarcoma Research Articles

Delimiting CD34+ Stromal Cells/Telocytes Are Resident Mesenchymal Cells That Participate in Neovessel Formation in Skin Kaposi Sarcoma.

Kaposi sarcoma (KS) is an angioproliferative lesion in which two main KS cell sources are currently sustained: endothelial cells (ECs) and mesenchymal/stromal cells. Our objective is to establish the tissue location, characteristics and transdifferentiation steps to the KS cells of the latter. For this purpose, we studied specimens of 49 cases of cutaneous KS using immunochemistry and confocal and electron microscopy. The results showed that delimiting CD34+ stromal cells/Telocytes (CD34+SCs/TCs) in the external layer of the pre-existing blood vessels and around skin appendages form small convergent lumens, express markers for ECs of blood and lymphatic vessels, share ultrastructural characteristics with ECs and participate in the origin of two main types of neovessels, the evolution of which gives rise to lymphangiomatous or spindle-cell patterns-the substrate of the main KS histopathological variants. Intraluminal folds and pillars (papillae) are formed in the neovessels, which suggests they increase by vessel splitting (intussusceptive angiogenesis and intussusceptive lymphangiogenesis). In conclusion, delimiting CD34+SCs/TCs are mesenchymal/stromal cells that can transdifferentiate into KS ECs, participating in the formation of two types of neovessels. The subsequent growth of the latter involves intussusceptive mechanisms, originating several KS variants. These findings are of histogenic, clinical and therapeutic interest.

Tumors after kidney transplantation: a population study

One of the main causes of post-transplant-associated morbidity and mortality is cancer. The aims of the project were to study the neoplastic risk within the kidney transplant population and identify the determinants of this risk. A cohort of 462 renal transplant patients from 2010 to 2020 was considered. The expected incidence rates of post-transplant cancer development in the referenced population, the standardized incidence ratios (SIR) taking the Italian population as a comparison, and the absolute risk and the attributable fraction were extrapolated from these cohorts of patients. Kidney transplant recipients had an overall cancer risk of approximately three times that of the local population (SIR 2.8). A significantly increased number of cases were observed for Kaposi’s sarcoma (KS) (SIR 195) and hematological cancers (SIR 6.8). In the first 3 years post-transplant, the risk to develop either KS or hematological cancers was four times higher than in the following years; in all cases of KS, the diagnosis was within 2 years from the transplant. Post-transplant immunosuppression represents the cause of 99% of cases of KS and 85% of cases of lymphomas, while only 39% is represented by solid tumors. Data related to the incidence, the percentages attributable to post-transplant immunosuppression, and the time of onset of neoplasms, particularly for KS and hematological tumors could help improve the management for the follow-up in these patients.

The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi's Sarcoma Tumors during Antiretroviral Therapy.

Epidemic Kaposi's sarcoma (KS), defined by co-infection with Human Herpes Virus 8 (HHV-8) and the Human Immunodeficiency Virus (HIV), is a major cause of mortality in sub-Saharan Africa. Antiretroviral therapy (ART) significantly reduces the risk of developing KS, and for those with KS, tumors frequently resolve with ART alone. However, for unknown reasons, a significant number of KS cases do not resolve and can progress to death. To explore how HIV responds to ART in the KS tumor microenvironment, we sequenced HIV env-nef found in DNA and RNA isolated from plasma, peripheral blood mononuclear cells, and tumor biopsies, before and after ART, in four Ugandan study participants who had unresponsive or progressive KS after 180-250 days of ART. We performed immunohistochemistry experiments to detect viral proteins in matched formalin-fixed tumor biopsies. Our sequencing results showed that HIV diversity and RNA expression in KS tumors are maintained after ART, despite undetectable plasma viral loads. The presence of spliced HIV transcripts in KS tumors after ART was consistent with a transcriptionally active viral reservoir. Immunohistochemistry staining found colocalization of HIV Nef protein and tissue-resident macrophages in the KS tumors. Overall, our results demonstrated that even after ART reduced plasma HIV viral load to undetectable levels and restored immune function, HIV in KS tumors continues to be transcriptionally and translationally active, which could influence tumor maintenance and progression.

Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000–2018)

Race and Ethnicity, Stage-Specific Mortality, and Cancer Treatment in Esophageal and Gastric Cancers: Surveillance, Epidemiology, and End Results (2000–2018)

Iatrogenic Kaposi sarcoma of the small bowel in Crohn’s disease following short-term use of immunomodulators: a case report and review of the literature

BackgroundKaposi sarcoma is a vascular tumor highly related to human herpesvirus-8 and Kaposi sarcoma–associated herpesvirus. Kaposi sarcoma usually manifests as skin or mucosal lesions; involvement in visceral organs such as the gastrointestinal tract is rare. Kaposi sarcoma can occur in immunocompromised patients receiving immunosuppressive therapy, in which case it is known as iatrogenic Kaposi sarcoma or drug-induced Kaposi sarcoma. Intestinal Kaposi sarcoma in patients with inflammatory bowel disease is extremely rare.Case presentationA 46-year-old East Asian male with recently diagnosed Crohn’s disease was administered azathioprine and prednisolone; however, the patient complained of persistent abdominal pain and diarrhea following treatment. Endoscopy revealed small bowel Kaposi sarcoma. The patient was treated with systemic chemotherapy successfully without relapse.ConclusionsThis is the fifth case of Kaposi sarcoma developed over the small intestine in a patient with Crohn’s disease following administration of immunomodulators. Additionally, this case indicated that even short-term immunomodulator use can induce Kaposi sarcoma in patients with inflammatory bowel disease. Thus, in patients with inflammatory bowel disease, if symptoms are aggravated or do not abate after immunomodulators prescription, and before intending to upgrade immunomodulators, endoscopy should be considered. Finally, chemotherapy can also be considered if both medication withdrawal and surgical intervention are not feasible.

Demographic profile, management, and survival of primary Gastrointestinal Kaposi Sarcoma: A USA Nationwide SEER-based study

Kaposi Sarcoma (KS) is a Human Herpes Virus-8 (HHV-8) associated angio-proliferative disorder commonly seen in patients with HIV. It most commonly involves the skin as classic purple lesions but occasionally involves the gastrointestinal (GI) tract. To date, published data is scarce on primary GI KS. Using a national database, this study analyzes the incidence, demographics, and survival of primary GI KS. We conducted a retrospective analysis (1975–2019) on biopsy-proven primary GI KS cases from 17 registries from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. A total of 685 patients with GI KS were identified. Female gender, Non-Hispanic Asian or Pacific Islander (NHAPI), married marital status, and large bowel site-specific primary KS to have better overall survival. Luminal gastrointestinal KS was more frequent (84.96%) than solid organ involvement (3.07% of all cases). This study is the most extensive population-based study about the epidemiological and survival data of patients with primary GI KS, revealing GI KS to be a young male disease with best outcomes in the large bowel and anal canal KS while inferior outcomes in extraintestinal GI KS.

PULMONARY KAPOSI SARCOMA WITH ASSOCIATED RECURRENT CHYLOTHORAX

SESSION TITLE: Pneumothorax, Chylothorax, and Pleural Effusion Case PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: AIDS related Kaposi Sarcoma (KS) is an endothelial malignancy associated with HHV8 infection. It is the most common malignancy in patients with AIDS. Pulmonary KS is uncommon and rarely causes pleural effusions, particularly chylothorax. Here we present a case of recurrent chylothorax leading to diagnosis of pulmonary KS by pleural biopsy.CASE PRESENTATION: 40-year-old male with HIV/AIDS on HAART therapy and KS was referred for pleural effusion. He was previously treated with Doxil for gastrointestinal KS, but stopped due to neutropenia. He had persistent shortness of breath and occasional night sweats. A thoracentesis was performed, and fluid studies were consistent with a chylothorax. He had a recurrent pleural effusion two months later, and he underwent right sided pleuroscopy with pleural biopsies, talc pleurodesis, and tunneled pleural catheter placement. Diffuse hemorrhagic lesions throughout the right lung, and a raised plaque like lesion along the parietal pleura were seen during pleuroscopy. Biopsy of the parietal pleural was consistent with metastatic KS. He will discuss treatment with his oncologist.DISCUSSION: Pulmonary KS is uncommon and rarely causes pleural effusions, particularly chylothorax. Thoracoscopy is usually not needed to diagnose pulmonary KS as it should only affect visceral pleura. As in this case, thoracoscopy is typically used to assist with patient's symptoms and rule out other causes of an effusion. This is a rare case of KS causing chylothorax requiring thoracoscopy and biopsies for diagnosis.CONCLUSIONS: Here we present a case of pulmonary KS with accompanying chylothorax. This is not a typical presentation or path to diagnosis for pulmonary KS.Reference #1: Cherian S, Umerah OM, Tufail M, et al. Chylothorax in a patient with HIV-related Kaposi's sarcoma. BMJ Case Reports CP2019;12:e227641.Reference #2: Ramos A, Granado J, et al. Pulmonary Kaposi Sarcoma - An atypical clinical presentation. International Journal of Infectious Disease. 2022;115:185-188.Reference #3: Pandya K, Lal C, et al. Bilateral Chylothorax with Pulmonary Kaposi's Sarcoma. Chest. 1988;94(6):1316-1317.DISCLOSURES: No relevant relationships by Harshesh AminNo relevant relationships by Yanglin GuoNo relevant relationships by John HeneganNo relevant relationships by Rachel MullinsNo relevant relationships by Randolph Ross SESSION TITLE: Pneumothorax, Chylothorax, and Pleural Effusion Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: AIDS related Kaposi Sarcoma (KS) is an endothelial malignancy associated with HHV8 infection. It is the most common malignancy in patients with AIDS. Pulmonary KS is uncommon and rarely causes pleural effusions, particularly chylothorax. Here we present a case of recurrent chylothorax leading to diagnosis of pulmonary KS by pleural biopsy. CASE PRESENTATION: 40-year-old male with HIV/AIDS on HAART therapy and KS was referred for pleural effusion. He was previously treated with Doxil for gastrointestinal KS, but stopped due to neutropenia. He had persistent shortness of breath and occasional night sweats. A thoracentesis was performed, and fluid studies were consistent with a chylothorax. He had a recurrent pleural effusion two months later, and he underwent right sided pleuroscopy with pleural biopsies, talc pleurodesis, and tunneled pleural catheter placement. Diffuse hemorrhagic lesions throughout the right lung, and a raised plaque like lesion along the parietal pleura were seen during pleuroscopy. Biopsy of the parietal pleural was consistent with metastatic KS. He will discuss treatment with his oncologist. DISCUSSION: Pulmonary KS is uncommon and rarely causes pleural effusions, particularly chylothorax. Thoracoscopy is usually not needed to diagnose pulmonary KS as it should only affect visceral pleura. As in this case, thoracoscopy is typically used to assist with patient's symptoms and rule out other causes of an effusion. This is a rare case of KS causing chylothorax requiring thoracoscopy and biopsies for diagnosis. CONCLUSIONS: Here we present a case of pulmonary KS with accompanying chylothorax. This is not a typical presentation or path to diagnosis for pulmonary KS. Reference #1: Cherian S, Umerah OM, Tufail M, et al. Chylothorax in a patient with HIV-related Kaposi's sarcoma. BMJ Case Reports CP2019;12:e227641. Reference #2: Ramos A, Granado J, et al. Pulmonary Kaposi Sarcoma - An atypical clinical presentation. International Journal of Infectious Disease. 2022;115:185-188. Reference #3: Pandya K, Lal C, et al. Bilateral Chylothorax with Pulmonary Kaposi's Sarcoma. Chest. 1988;94(6):1316-1317. DISCLOSURES: No relevant relationships by Harshesh Amin No relevant relationships by Yanglin Guo No relevant relationships by John Henegan No relevant relationships by Rachel Mullins No relevant relationships by Randolph Ross

S2431 A Rare Case of Esophageal Kaposi Sarcoma Causing Dysphagia

Introduction: Kaposi sarcoma (KS) is an angioproliferative disorder(low grade vascular tumor) caused by human herpesvirus-8 in immunocompromised patients. The disease is multifocal, ranging from indolent skin manifestations to extensive visceral involvement. We are describing a rare case of esophageal KS causing dysphagia. Case Description/Methods: A 57-year-old bisexual male with a medical history of hypertension, syphilis and recent diagnosis of HIV (untreated) admitted for hypotension, tachycardia, nausea, vomiting,hemoptysis and dysphagia to soilds. He was noted to have oropharyngeal lesions and biopsy of the lesions were obtained. An EGD performed for evaluation of dysphagia (denied odynophagia) showed circumferential erythema, purplish plaques and friability of the esophagus. Biopsies were obtained from esophagus. Pathology from tongue, gingiva, proximal and distal esophagus returned positive for Kaposi sarcoma with positive staining for HHV-8 and CD31. CD4 count was 31/uL and HSV8 PCR showed 1,000,000 copies. Patient was treated with Bictegravir, emtricitabine and tenofovir alafenamide. Hematology was consulted for potential pulmonary KS and patient was started on liposomal doxorubicin. He developed Ventricular fibrillation and cardiac arrest. He was revived and intubated. Patient improved initially but developed neutropenic fever. Infectious disease treated him with empirical antibiotics and antivirals. Patient further developed Castleman’s disease, respiratory failure, acute kidney failure requiring CRRT, and altered mental status. Despite aggressive measures patient did not survive (Figure). Discussion: AIDS-related KS varies in clinical progression and occurs in 20% of patients with AIDS. The CD4 count will typically be less than 150 cells per cubic millimeter with a high viral load ranging from greater than 10,000 copies per millimeter. Gastrointestinal manifestation is the most common extra-cutaneous site of KS in AIDS-related cases though rarely does it occur without cutaneous involvement. The majority of the patients are asymptomatic, roughly 75%. Symptomatic patients present with nonspecific findings such as abdominal discomfort, cramps, nausea, vomiting, diarrhea, and upper or lower GI bleed. KS lesions causing dysphagia are extremely rare. The mainstay of therapy is combined antiretroviral therapy (ART). Local intralesional chemotherapy can be utilized to manage limited lesions. Systemic therapy with liposomal anthracyclines is recommended for patients with advanced or rapidly progressive disease.Figure 1.: Kaposi Sarcoma Lesions.

Kaposi's sarcoma in people living with HIV/aids in a public referral hospital in Peru.

Kaposi's sarcoma (KS) is the most frequent cancer in people living with HIV. Research on this condition is scarce in the region, therefore, this article aimed to describe the demographic, clinical and therapeutic characteristics of patients with HIV who developed KS at the Cayetano Heredia Hospital between 2000 and 2018. A total of 129 KS cases were identified, with a median age of 33 years, predominantly males with 92% (119/129), and mostly men who have sex with men (MSM). The median time from HIV diagnosis to KS diagnosis was five months, associated with a CD4 lymphocyte count of 64 cells/μL (IQR: 33-185) at KS diagnosis. Cutaneous involvement was the most common presentation; however, at least half also had the visceral form.

Cancer in patients with and without HIV infection in the national cancer registry of Rwanda.

As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time. Retrospective cohort study. Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV-). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis. Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV- individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV ( P < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs ( P < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time. The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.

Histologic Variants of Kaposi Sarcoma in the Gastrointestinal Tract: A Contemporary Multi-institutional Clinicopathologic Analysis of 46 Cases.

Kaposi sarcoma (KS) can pose diagnostic challenges in biopsy specimens. Multiple histologic variants of cutaneous KS have been described; however, the histomorphologic spectrum of gastrointestinal (GI) KS has not been systematically studied. This large series comprehensively evaluated 46 cases of KS involving the GI tract and identified 7 histomorphologic variants, some that have not been previously described. Five of them are inconspicuous but have unique morphologic patterns, including lymphangioma/lymphangiectatic-like (n=17), mucosal hemorrhage/telangiectatic-like (n=17), mucosal inflammation-like (n=15), granulation tissue-like (n=13), and mucosal prolapse-like (n=4) variants. These variants can be easily misdiagnosed or misinterpreted on routine examination if KS is not considered, and if the immunohistochemical stain for human herpesvirus-8 is not performed. The other 2 morphologic variants present as spindle cell proliferations and are the GI stromal tumor-like (n=8) and inflammatory myofibroblastic tumor-like (n=2). These variants raise a broad differential diagnosis of spindle cell tumors of the GI tract and could pose diagnostic challenges. In summary, GI KS lesions exhibit variable, often unconventional histomorphologic patterns. KS should be included in the differential diagnosis even if features of conventional KS are not seen, particularly in limited biopsies in immunocompromised patients, such as those with human immunodeficiency virus infection. Although the clinical significance of these morphologic variants is yet to be determined, they are nonetheless important from a diagnostic standpoint. Misdiagnosis and delay in appropriate management can be avoided by recognizing the morphologic diversity of GI KS and appropriately utilizing the human herpesvirus-8 immunohistochemical stain.

Kaposi’s Sarcoma Trends in the Era of Highly Active Antiretroviral Therapy in Zambia

AIDS-related Kaposi’s Sarcoma (KS) is a multi-centric angiogenic neoplastic proliferation predominantly seen in individuals with Human Immune Virus (HIV-1) infection and men who have sex with men. Although the incidences of aggressive KS have reduced following the introduction of Highly Active Antiretroviral Therapy (HAART) in the treatment of HIV infection, the effect of HAART rollout in relation to population KS incidence in Zambia remains unclear as cases of the malignancy have continued to be reported. This study, investigated the trends of KS in the era of HAART in Zambia. The researchers conducted a retrospective cross-sectional study. Three hundred and twentycases of HIV-infected individuals on HAART that developed KS between 2008 and 2017 were reviewed. Data was retrieved from the Zambia National Cancer Registry (ZNCR). Of the records reviewed, the researchers observed a sharp increase in KS cases from 5.6 per cent in 2008 to 21.2 per cent in 2014; from 2015 to 2017, there was a general decline in KS cases countrywide in both sexes from 13.1 per cent to 9.4 per cent. KS was more prevalent in Lusaka Province, while Western Province had the least number of cases. For each province, there were more males affected by KS than females. The researchers further observed that 19.1 per cent of the cases reviewed developed KS while on HAART, while 80.9 per cent developed KS before the commencement of HAART. The age group with the highest number of KS cases was 21-40 years, while the age group ≥ 80 had the least number of cases. Our data has shown that although there has been a general decline in KS cases across the ten provinces of Zambia in recent years, more efforts are still required to mitigate AIDS-related KS incidence and improve KS prognosis. There is a need to encourage efforts aimed at HIV infection prevention, wide coverage of HAART across the country, and KS awareness and screening.

BI12: A retrospective analysis of cases of Kaposi sarcoma in patients at a tertiary centre

BI12: A retrospective analysis of cases of Kaposi sarcoma in patients at a tertiary centre

Systematic analysis of Kaposi's sarcoma (KS)-associated herpesvirus genomes from a KS case-control study in Cameroon: Evidence of dual infections but no association between viral sequence variation and KS risk.

In sub-Saharan Africa, Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic, and Kaposi's sarcoma (KS) is a significant public health problem. Until recently, KSHV genotype analysis was performed using variable gene regions, representing a small fraction of the genome, and thus the contribution of sequence variation to viral transmission or pathogenesis are understudied. We performed near full-length KSHV genome sequence analysis on samples from 43 individuals selected from a large Cameroonian KS case-control study. KSHV genomes were obtained from 21 KS patients and 22 control participants. Phylogenetic analysis of the K1 region indicated the majority of sequences were A5 or B1 subtypes and all three K15 alleles were represented. Unique polymorphisms in the KSHV genome were observed including large gene deletions. We found evidence of multiple distinct KSHV genotypes in three individuals. Additionally, our analyses indicate that recombination is prevalent suggesting that multiple KSHV infections may not be uncommon overall. Most importantly, a detailed analysis of KSHV genomes from KS patients and control participants did not find a correlation between viral sequence variations and disease. Our study is the first to systematically compare near full-length KSHV genome sequences between KS cases and controls in the same endemic region to identify possible sequence variations associated with disease risk.

Kaposi Sarcoma of the Larynx: A Systematic Review.

Kaposi sarcoma (KS) of the larynx is a rare disease with few cases reported in the literature. This study aims to provide a comprehensive review of laryngeal KS, including patient characteristics, treatment, and clinical outcomes. PubMed, CINAHL, SCOPUS, and Cochrane Library. A systematic review of the published English literature was conducted. An electronic search and bibliographic examination of articles pertaining to laryngeal KS were performed. Demographic data, tumor site, treatment strategies, follow-up, and outcome were analyzed. A total 77 cases from 50 articles were included in the review. The mean age was 47.6 years (range, 8-81). There was an 8.6:1 male:female ratio. The most common presenting symptoms were dyspnea (n = 35) and hoarseness (n = 25). Laryngeal KS arose most frequently in the supraglottic region (n = 16). Chemotherapy alone (n = 27) was the most common treatment modality in patients with AIDS-associated KS, and surgical excision alone (n = 7) was most common in patients with other subtypes of KS (eg, classic, transplant associated). Average follow-up was 20.4 months (range, 0.75-120). Most patients with AIDS-associated KS died of other causes (n = 25), but most patients with other subtypes of KS were alive with no evidence of disease at follow-up (n = 13). This review contains the largest pool of laryngeal KS cases to date. Long-term outcomes were generally unfavorable, often due to advanced HIV disease at the time of diagnosis.

Lifestyle factors associated with sex differences in Kaposi sarcoma incidence among adult black South Africans: A case-control study

Kaposi Sarcoma (KS) is endemic in several countries in Southern and Eastern Africa, relatively rare worldwide but a leading cancer among people living with HIV. KS has always been more common in adult males than females. We assessed the prevalence of known cancer modifying factors (parity, hormonal contraceptive use in females, sex-partners, smoking and alcohol consumption in both sexes), and their relationship to KS, and whether any of these could account for the unequal KS sex ratios. We calculated logistic regression case-control adjusted odds ratios (ORadj), and 95% confidence intervals (95%CI), between KS and each of the modifying factors, using appropriate comparison controls. Controls were cancer types that had no known relationship to exposures of interest (infection or alcohol or smoking or contraceptive use). The majority of the 1275 KS cases were HIV positive (97%), vs. 15.7% in 10,309 controls. The risk of KS among those with HIV was high in males (ORadj=116.70;95%CI=71.35–190.88) and females (ORadj=93.91;95%CI=54.22–162.40). Among controls, the prevalence of smoking and alcohol consumption was five and three times higher in males vs. females. We found a positive association between KS and heavy vs. non-drinking (ORadj=1.31;95%CI=1.03–1.67), and in current heavy vs. never smokers (ORadj=1.82;95%CI=1.07–3.10). These associations remained positive for alcohol consumption (but with wider CIs) after stratification by sex, and restriction to HIV positive participants. We found no evidence of interactions of smoking and alcohol by sex. Smoking and alcohol consumption may provide a possible explanation for the KS sex differences, given both exposures are more common in men, but confounding and bias cannot be fully ruled out. The role smoking and alcohol play in relation to viral loads of HIV/KSHV, differences in immunological responses or other genetic differences between males and females warrant further studies.

Molecular Mechanisms of Kaposi Sarcoma Development.

Simple SummaryThere are at least four forms of Kaposi’s sarcoma (KS) with the ‘HIV’-related form being the most aggressive and can involve mucosae or visceral organs. Kaposi’s sarcoma-associated herpes virus (KSHV) is the underlying cause of this disease. It can infect endothelial and/or mesenchymal cells and establish a latent phase in host cells in which latency proteins and various non-coding RNAs (ncRNAs) play a complex role in proliferation and angiogenesis. It also undergoes periods of sporadic lytic reactivation that are key for KS progression. Complex interactions with the microenvironment with production of inflammatory cytokines and paracrine signaling is a standout feature of KS development and maintenance. KSHV impairs the immune response by various mechanisms such as the degradation of a variety of proteins involved in immune response or binding to cellular chemokines. Treatment options include classical chemotherapy, but other novel therapies are being investigated.Kaposi’s sarcoma (KS) is a heterogeneous angioproliferative tumor that generally arises in the skin. At least four forms of this disease have been described, with the ‘HIV’-related form being the most aggressive and can involve mucosae or visceral organs. Three quarters of KS cases occur in sub-Saharan Africa (SSA) as geographic variation is explained by the disparate prevalence of KS-associated herpes virus (KSHV), which is the underlying cause of this disease. It can infect endothelial and/or mesenchymal cells that consequently transdifferentiate to an intermediate state. KSHV establishes a latent phase in host cells in which latency proteins and various non-coding RNAs (ncRNAs) play a complex role in proliferation and angiogenesis. It also undergoes periods of sporadic lytic reactivation triggered by various biological signals in which lytic stage proteins modulate host cell signaling pathways and are key in KS progression. Complex interactions with the microenvironment with production of inflammatory cytokines with paracrine signaling is a standout feature of KS development and maintenance. KSHV impairs the immune response by various mechanisms such as the degradation of a variety of proteins involved in immune response or binding to cellular chemokines. Treatment options include classical chemotherapy, but other novel therapies are being investigated.

Disseminated Pulmonary Kaposi Sarcoma After Lung Transplantation: The Increased Risk Donor

<h3>Introduction</h3> Kaposi sarcoma (KS) is a rare complication after lung transplantation (LTx). It is caused by human herpes virus 8 (HHV-8). We report a case of primary disseminated pulmonary KS after LTx from an increased risk donor. <h3>Case Report</h3> A 66-year-old male with end-stage COPD underwent a bilateral LTx from an increased risk donor with positive HBsAb, HBcAb and Lues Ab, in November 2020. Apart from Valganciclovir (vGCV) and co-trimoxazole, entecavir and benzylpenicillin were given as prophylaxis. Routine immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil (MMF) and prednisolone. vGCV prophylaxis was discontinued at 3 months (CMV-positive donor and recipient). The patient was treated effectively for acute rejection with pulse methylprednisolone in February 2021. Unfortunately, he was readmitted with dyspnea and lung function decline in April 2021. CT-scan showed bilateral consolidations and pleural thickening and the PET-scan showed an intense uptake in both lungs and pleura. Transthoracic needle biopsy showed HHV-8 positive spindle cell lesions. Subsequently, our patient developed skin lesions on his chest and in his mouth compatible with KS (biopsy-proven). In retrospect, the recipient was HHV-8 seronegative before LTx. Therefore, the diagnosis primary HHV-8 infection leading to disseminated pulmonary Kaposi sarcoma was made. Which appeared after cessation of the vGCV prophylaxis. Valganciclovir was initiated and immunosuppression was adjusted: MMF discontinued and tacrolimus switched to sirolimus (target through levels 15 µg/l). Nevertheless, KS was progressive and liposomal doxorubicin 20mg/m2 was started. Our patient deteriorated and was transferred to the ICU for intubation. Bronchoscopy revealed brown endobronchial lesions compatible with KS. The effect of the treatment could not be assessed, because the patient decided to refuse further treatment. He died soon after his decision was made. <h3>Summary</h3> Scarcity of donor organs led to the acceptance of an increased risk donor. Prophylaxis against hepatitis B and Lues was given, but after discontinuation of vGCV our patient developed a primary HHV-8 infection leading to disseminated KS and ultimately the death of our patient. HHV-8 testing of donor serum and lifelong prophylaxis might have prevented this clinical course and should be considered in recipients of increased risk donors.

A Case of Neglected Classıc Kaposı’s Sarcoma

Kaposi's sarcoma (KS) is a rare disease in the community. It was first described in 1872 as an idiopathic, multipigmented sarcoma of the skin [1]. It is a vascular or lymphatic-focused tumor type originating from the endothelium, caused by Human Herpes Virus 8 (HHV8), called KS-associated herpes virus (KSHV) [2]. There are 4 clinical subtypes of the disease. These are: Classical KS, African endemic KS, iatrogenic KS, and AIDS-related (epidemic) KS. It usually occurs with pink-red patch and blue-purple-black nodule, polyp or plaques. Most of the cases in classical KS are over 50 years old. Although the female/male ratio varies between studies, it is more common in males [3]. Here, a neglected case of Classic KS is presented.

Burden of Kaposi sarcoma according to HIV status: A systematic review and global analysis.

In 2020, over 34 000 cases of Kaposi sarcoma (KS) were estimated globally, all attributable to KS herpesvirus (KSHV). Prior to the HIV epidemic, KS already existed in KSHV endemic regions, notably in sub-Saharan Africa (SSA). The HIV epidemic has vastly increased the KS burden. We developed a methodology to provide global estimates of KS burden according to HIV status. A systematic review identified studies reporting HIV prevalence in consecutive KS series. Pooled estimates of HIV prevalence, by country or UN subregion, were used to calculate population-attributable fraction (PAF) and these were applied to IARC's GLOBOCAN 2020 to estimate burden and incidence of HIV-attributable and non-HIV-attributable KS. We identified 55 eligible studies, reporting HIV prevalence ranging from ≤5% to ≥95%. Approximately 80% of KS in SSA was estimated attributable to HIV, vs ~50% in the rest of the world. By applying PAFs to national GLOBOCAN estimates, an estimated 19 560 KS cases attributable to HIV were diagnosed in SSA in 2020 (~80% of the worldwide burden), vs 5064 cases of non-HIV-attributable KS (~60% of the worldwide burden). Incidence of HIV-attributable KS was highest in Southern Africa (6.0 cases per 100 000) and Eastern Africa (3.4), which were also the world regions with highest incidence of non-HIV-attributable KS (0.4 and 1.0 cases per 100 000, respectively). This first systematic effort to produce a global picture of KS burden stratified by HIV status highlights the continuing important burden of HIV-attributable KS in SSA, even in the era of combined antiretroviral therapy.