Eyelid Kaposi Sarcoma in HIV-Negative Patient

Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.

Genotypic analysis on the ORF-K1 gene of human herpesvirus 8 from patients with Kaposi's sarcoma in Xinjiang,China

Human herpesvirus 8 （HHV-8） is thought to be essential for the development of all forms of Kaposi＇s sarcoma （KS）. HHV-8 DNA is present virtually in all KS tumor biopsy samples. Genes at both ends of the HHV-8 genome have been shown to vary considerably. Seven major molecular subtypes of HHV-8 were defined based on the amino acid sequence of the open reading frame K1 （ORF-K1）, generally known as A, B, C, D, E, F, and Z. Most strains collected worldwide were clustered into two subtypes （A and C）. Here, the K1/VRI region of HHV-8 was amplified by nested PCR in 22 （81.48%） of 27 cases from Xinjiang Uygur Autonomous Region, a province in northwestern China. Phylogenetic analysis on the basis of the K1/VR1 amino acid sequence indicated that the majority of these KS patients were infected by subtype C HHV-8 （n = 18, including 15 belonging to the C2 group）, and several by subtype A （n = 4, including 3 being the A1 group）. This is the first report of subtype A HHV-8 in China. Furthermore, the correlations between different forms and lesions of KS and different subtypes of HHV-8 were analyzed. The findings showed that subtype A HHV-8 resulted in significantly more frequent mucosal KS lesions than subtype C. However, there was no obvious correlation between different forms of KS and different subtypes of HHV-8.

Hepatic Kaposi sarcoma: A case report and review of the literature

Kaposi sarcoma(KS) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. As opposed to the well-described cutaneous manifestations and pulmonary complications of KS, hepatic KS is rarely reported before death as most patients with hepatic KS do not manifest symptoms or evidence of liver injury. In patients with acquired immune deficiency syndrome, hepatic involvement of KS is present in 12%-24% of the population on incidental imaging and in approximately 35% of patients with cutaneous KS if an autopsy was completed after their death. Patients with clinically significant hepatic injury due to hepatic KS usually have an aggressive course of disease with hepatic failure often progressing to multi-organ failure and death. Here we report an unusual presentation of acute liver injury due to hepatic KS and briefly review the published literature on hepatic KS.

The effect of ABV regimen on CD4 lymphocyte count in patients with advanced HIV related Kaposi’s sarcoma

Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi's sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemotherapy with ABV regimen which was administered at 3 weekly intervals for 6 cycles. For each patient CD4 cell count was done before starting chemotherapy and after finishing 6 cycles of chemotherapy. The difference of CD4 cell counts pre chemotherapy and post chemotherapy was compared with the clinical progress of the patients after 6 cycles of chemotherapy. Results: The overall clinical remission was shown in 93.7% patients. Progressive disease (PD) and no change in clinical condition (NC) was shown in 6.3% patients. The increase in CD4 cell count post chemotherapy was found in 89.8% patients and the decrease in CD4 cell count was seen in 10.2% patients. The difference of the mean CD4 cell counts for patients in group CR + PR (complete relief + partial relief) before and after chemotherapy was highly significant. The difference of the mean CD4 cell counts for patients in group NC + PD before and after chemotherapy was not significant. The difference in CD4 cell counts in CR + PR and NC + PD groups before and after chemotherapy was highly significant. Conclusion: The HIV related KS patients on HAART benefit from the chemotherapy as it increases the CD4 cell count and it has positive impact on clinical remission of KS.

Coexistent Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes after pediatric liver transplantation:A case report

BACKGROUND Kaposi sarcoma and post-transplant lymphoproliferative disorder have been occasionally reported in post-liver transplant patients.However,the simultaneous occurrence of these two diseases in the same lymph nodes is very rare.CASE SUMMARY We report the case of a 19-mo-old boy,who presented with intermittent fever and enlarged cervical lymph nodes after liver transplantation.Six cervical lymph nodes were biopsied,and the histopathological examinations revealed multifocal hyperplasia of spindle cells around small blood vessels,extravasated erythrocytes,and heavy infiltration of plasma cells in the cortex and medulla of the lymph nodes.The immunohistochemical analyses of spindle cells revealed positive expression of CD34,CD31,erythroblast transformation-specific-related gene,friend leukemia integration 1,and human herpesvirus-8.The lymphoproliferative lesions expressed CD38,CD138,and multiple myeloma 1.Epstein-Barr encoded RNA in situ hybridization demonstrated Epstein-Barr virus-positive lymphoid cells.Finally,we diagnosed the coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder(plasmacytic hyperplasia)in the same lymph nodes.Treatment strategy included anti-CD20 monoclonal antibody(rituximab)and discontinuation of the immunosuppressant therapies.Lymph node biopsies during follow-up examinations revealed lymphoid hyperplasia.CONCLUSION The rare coexistence of Kaposi sarcoma and post-transplant lymphoproliferative disorder in the same lymph nodes post-liver transplantation possibly associates with immunodeficiency and Epstein-Barr virus and human herpesvirus-8 coinfection.

Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection

Diffuse intestinal Kaposi＇s sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 （HHV8） and the diagnosis had to be changed to diffuse intestinal Kaposi＇s sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi＇s sarcoma should be determined, as distinct treatment is indicated.

Angiogenesis,Kaposi’s Sarcoma and Kaposi’s Sarcoma-associated Herpesvirus

Tumor angiogenesis is the uncontrolled growth of blood vessels in tumors,serving to supply nutrients and oxygen,and remove metabolic wastes. Kaposi’s sarcoma (KS),a multifocal angioproliferative disorder characterized by spindle cell proliferation,neo-angiogenesis,inflammation,and edema,is associated with infection by Kaposi's sarcoma-associated herpesvirus (KSHV). Recent studies indicate that KSHV infection directly promotes angiogenesis and inflammation through an autocrine and paracrine mechanism by inducing pro-angiogenic and pro-inflammatory cytokines. Many of these cytokines are also expressed in KS lesions,implicating a direct role of KSHV in the pathogenesis of this malignancy. Several KSHV genes are involved in KSHV-induced angiogenesis. These studies have provided insights into the pathogenesis of KS,and identified potential therapeutic targets for this malignancy.

Mathematical Model of Classical Kaposi’s Sarcoma

In this paper, the global properties of a classical Kaposi’s sarcoma model are investigated. Lyapunov functions are constructed to establish the global asymptotic stability of the virus free and virus (or infection) present steady states. The model considers the interaction of B and progenitor cells in the presence of HHV-8 virus. And how this interaction ultimately culminates in the development of this cancer. We have proved that if the basic reproduction number, R0 is less than unity, the virus free equilibrium point, ε0, is globally asymptotically stable (GAS). We further show that if R0 is greater than unity, then both the immune absent and infection persistent steady states are GAS.

Splenic Kaposi’s sarcoma in a human immunodeficiency virusnegative patient:A case report

BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development of KS is associated with human herpes virus 8(i.e.HHV8)infections.Sporadic KS cases have mainly been found in Africa.Isolated splenic KS in Asia has rarely been reported.We present here a case of KS primarily involving the spleen in a human immunodeficiency virus(HIV)-negative Chinese patient.CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort,reduced food intake and weight loss.Medical examination revealed that the patient had moderate anemia,a low platelet count,slight fatty liver and a huge mass in the spleen.Spleen lymphoma was considered.An anti-HIV test was negative.The whole spleen was surgically excised.The final pathological diagnosis was nodular stage spleen KS,and the patient underwent total splenectomy.He recovered well and was discharged from hospital 12 d after surgery.Two weeks later,the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSION KS is difficult to diagnose and pathological examination is necessary.KS has a poor prognosis and should be diagnosed and treated early to improve survival.

Primary Effusion Lymphoma in a HIV-1/2-Infected Patient

Background: Primary effusion lymphoma (PEL) is a lymphoid proliferation related to Kaposi sarcoma herpesvirus 8/human herpesvirus 8 (KSHV/HHV8) that affects mainly human immunodeficiency virus (HIV) infected individuals but can also occur in other immunodeficiency settings. It is characterized by lymphomatous effusions in different serous body cavities without the presence of a detectable tumor mass. The diagnosis is challenging and the clinical outcomes are poor. Aim: The aim of this paper is to report a rare case of PEL in a man who have sex with women (MSW) with HIV-1/2 infection, history of visceral Kaposi sarcoma (KS) and the development of a seronegative arthritis previous to the lymphoproliferative disease diagnosis. PEL presented with ascites, was treated with high-dose chemotherapy and autologous stem cell transplantation, with a good clinical outcome. Case Presentation: We describe a case of a 48-year-old HIV-1/2-infected patient from a high HHV8 seroprevalent country, hospitalized following a three-month history of increased abdominal volume and general constitutional symptoms. Laboratory data revealed normocytic normochromic anemia and a high level of lactate dehydrogenase. A diagnostic paracentesis was performed with cytology compatible with high-grade B-cell lymphoma. Peritoneal fluid cytology showed large lymphoid cells expressing leucocyte-common antigen CD45 without expression of the CD20 antigen (B-lymphocytes) and positivity for HHV8 by immunocytochemical staining, compatible with the diagnosis of PEL.

AIDS and associated malignancies

AIDS associated malignancies （ARL） is a major complication associated with AIDS patients upon irnmunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy （ARV）, the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi＇s sarcoma （KS）, Hodgkin＇s disease （HD） and non-Hodgkin＇s lymphoma （NHL）. The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV- 1 seronegative patients. For example nearly haft of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus （EBV） or human herpesvirus-8 （HHV-8）/Kaposi＇s sarcoma associated herpesvirus （KSHV）. The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.

Malignant hepatic vascular tumors in adults: Characteristics,diagnostic difficulties and current management

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation(LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma(HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation AssociationEuropean Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma(HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient.Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches,alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

Establishment of method for seroepidermiological detection of human herpes virus 8 infection by using the fusion protein in the prokaryotic expression system as antigen for testing

To establish a sensitive and specific method for seroepidermiological detection of human her- pes virus 8(HHV-8)infection,three potent antigenic proteins encoded by open reading frames(ORFs) K8.1,65 and 73C in genome of HHV-8 were produced as glutathione S-transferase fusion protein in the prokaryotic expression system and was used as antigen for testing.The recombinant fusion protein ex- pressed in the prokaryotic expression vector E.coli BL21 was purified by glutathione Sepharose 4B affin- ity chromatography and was quantitated with SDS-PAGE.All these 3 fusion proteins produced in the pro- karyotic expression system showed good immunogenicity as demonstrated by Western blotting and could be recognized by mixed sera of patients with Kaposi′s sarcoma(KS).The immuno-reactivities of the single or compound fusion protein were determined by means of ELISA and compared with the traditional immu- nofluorescence assay(IFA)to determine their sensitivity and specificity of the test.It was demonstrated that the sensitivity of mixed-antigen ELISA method was significantly higher than that of IFA(81.8% vs 34.4%),while the specificity of the former was demonstrated to be 97.9%.The coincidence of the de- tection rate between these two methods was considerably high,approaching up to 90.0%.These results suggest that the mixed antigen ELISA assay appears to be a sensitive and specific method for sero-epide- miological detection of human herpesvirus 8 infection.

Bullous Pemphigoid With Nail Damage Associated With Kaposi Sarcoma:A Case Report

Introduction:Bullous pemphigoid is an acquired autoimmune bullous skin disease that occurs in the elderly,and nail involvement is relatively rare.Kaposi sarcoma(KS) is a rare opportunistic tumor in patients with iatrogenic immunosuppression and is rarely associated with autoimmune bullotic disease.Case presentation:The patient was diagnosed with bullous pemphigoid based on her history,bullous pemphigoid antibody,and skin pathological examination.And nail involvement occurred 20 days prior to the recurrence of the disease.Moreover,KS occurred during high-dose glucocorticoid therapy in this patient.Discussion:The patient was admitted to hospital because of a five-month history of erythema and blisters and a one-month history of nodules and plaques.The diagnosis of bullous pemphigoid was followed by treatment with glucocorticoids and intravenous gamma globulin.During treatment,the disease recurred due to discontinuation of glucocorticoids.There were erythema and blisters all over the body,and purple nodules,plaques appeared in the base of some blisters.Pathological examination of nodules was consistent with KS.In addition,nail involvement occurred 20 days before recurrence.The particularity of this case lies in the simultaneous occurrence of nail involvement,bullous pemphigoid,and KS.Conclusion:Patients with autoimmune bullous skin disease may suddenly develop abnormal nails,and such patients should be vigilant about recurrence of the disease.Doctors should be aware of the possibility of KS when rapidly progressing purplish red plaques or nodules appear in patients receiving high doses of corticosteroids or immunosuppressants.

Prevalence of Kaposi's sarcoma-associated herpesvirus in Uygur and Han populations from the Urumqi and Kashgar regions of Xinjiang, China

Kaposi's sarcoma-associated herpesvirus(KSHV) is the infectious etiologic agent associated with Kaposi's sarcoma(KS), primary effusion lymphoma, and multicentric Castleman disease. It has been shown that high KSHV prevalence and high incidence of both classic KS and AIDSassociated KS are found mostly among people of Uygur ethnicity in Xinjiang, while people of Han ethnicity in Xinjiang have a higher KSHV seroprevalence than those of other Han populations in China's Mainland. However, it is still unclear why there is such geographical and population variation in KSHV distribution in China. In this work, we focused on the populations in the Kashgar region and Urumqi area, where a total of 1294 research subjects were randomly selected to investigate the potential correlation between KSHV prevalence and different ethnicities in endemic areas of Xinjiang, and to determine risk factors that may affect KSHV infection rates or KS incidence. We identified a high seroprevalence of KSHV and high peripheral blood DNA infection in the general Uygur and Han populations in both Urumqi and Kashgar regions of Xinjiang, and determined that advancing age, low education level, and stationary population status affect KSHV infection rates. Further, KSHV-positive Uygur participants were shown to have higher prevalence of neutralizing antibodies and neutralizing antibody titers than KSHV-positive Han participants.

Identification of human herpesvirus-8 in Kaposi＆#39;s sarcoma with bullous pemphigoid

Kaposi＆#39;s sarcoma （KS） is a rare,malignant vascular.tumor of the skin,mucosa,and viscera with an increased incidence in human immunodeficiency virus （HIV）-positive patients.According to the clinical characteristics and the affected population,four clinical types of KS have been described successively：classic,endemic to Africa,acquired immunodeficiency syndrome （AIDS）-associated,and immunosuppression associated type.Bullous pemphigoid （BP） is an acquired autoimmune bullous skin disease that frequently occurs in the elderly and is characterized by intraepidermal blisters and immunoglobulin G （IgG） deposits on the basement membrane.A few cases of KS have occurred in immunosuppressed patients with BP.Here,we report a Chinese female patient diagnosed with immunosuppression associated KS that was induced by the short-term use of immunosuppressive agents for BP.We also present a review of the literature on immunosuppressed KS with BP and discuss the potential role of human herpesvirus-8 （HHV-8） in the pathogenic mechanism.

SOX5 Regulates Cell Proliferation, Apoptosis, Migration and Invasion in KSHV-Infected Cells

Kaposi's sarcoma(KS) originates from vascular endothelial cells, with KS-associated herpesvirus(KSHV) as the etiological agent. SRY-box transcription factor 5(SOX5) plays different roles in various types of cancer, although its role in KS remains poorly understood. In this study, we identified the role of SOX5 in KS tissues and KSHV-infected cells and elucidated the molecular mechanism. Thirty-two KS patients were enrolled in this study. Measurement of SOX5 m RNA and protein levels in human KS tissues and adjacent control tissues revealed lower levels in KS tissues, with KS patients having higher SOX5 level in the early stages of the disease compared to the later stages. And SOX5 m RNA and protein was also lower in KSHV-infected cells(iSLK-219 and iSLK-BAC) than normal cells(iSLK-Puro). Additionally, SOX5 overexpression inhibited cell proliferation and promoted apoptosis and decreased KSHV-infected cell migration and invasion. Moreover, we found that SOX5 overexpression suppressed the epithelial-to-mesenchymal transition of KSHV-infected cells. These results suggest SOX5 is a suppressor factor during KS development and a potential target for KS treatment.