Cases Of Kaposi's Sarcoma Research Articles

Change in Pattern of Secondary Cancers After Kaposi Sarcoma in the Era of Antiretroviral Therapy

Studies performed in the 1980s and early 1990s have shown that people who develop Kaposi sarcoma (KS) are at higher risk of developing other cancers. The demographics of those affected with human immunodeficiency virus (HIV)/AIDS and KS have changed, and individuals with HIV/AIDS and KS now live longer. To test the hypothesis that the secondary cancers developing in patients with KS have changed in recent years and to assess the risk of secondary cancers after KS in different periods. Longitudinal data from 9 cancer registries in the Surveillance, Epidemiology, and End Results (SEER) database were used to identify cases of KS diagnosed from January 1973 to December 2013. The dates of the analysis were November 2016 to February 2017. The primary outcome was the development of secondary cancers in individuals with KS. Secondary cancers were considered only if diagnosed 2 months after a diagnosis of KS. Standardized incidence ratios (SIRs) were calculated for the development of new secondary cancers in the pre-AIDS era (1973-1979), pre-highly active antiretroviral therapy (HAART) era (1980-1995), and HAART era (1996-2013). Stratified analysis was then performed on a subset of the cases diagnosed from 1996 to 2013 based on age at diagnosis (<65 and ≥65 years), latency period between KS and the development of secondary cancers (1 year, 2-5 years, >5 to 10 years, and >10 years), and registries with higher vs lower reported rates of HIV/AIDS. Among 14 905 individuals with diagnosed KS, 13 721 (92.1%) were younger than 65 years at the time of diagnosis, and 14 356 (96.3%) were male. From 1980 to 1995, SIRs were 2.01 (95% CI, 1.00-3.60) for cancer of the rectum, 49.70 (95% CI, 33.53-70.94) for cancer of the anus, 4.98 (95% CI, 2.79-8.22) for cancer of the liver, 13.70 (95% CI, 2.82-40.03) for cancer of the cervix, 6.40 (95% CI, 2.76-12.60) for Hodgkin lymphoma, and 48.97 (95% CI, 44.85-53.36) for non-Hodgkin lymphoma. From 1996 to 2013, cancer of the anus, Hodgkin lymphoma, non-Hodgkin lymphoma, and cancer of the liver remained associated with KS, with the addition of the following significant SIRs: 6.99 (95% CI, 3.20-13.27) for cancer of the tongue, 10.28 (95% CI, 1.24-37.13) for cancer of the penis, and 17.62 (95% CI, 3.63-51.49) for acute lymphocytic leukemia. The SIR of developing any tumor after KS decreased significantly from 3.36 to 1.94 from the pre-HAART era to the HAART era. There has been a significant decline in the overall risk of secondary cancers after KS. Certain cancers, including acute lymphocytic leukemia, cancer of the tongue, and cancer of the penis, are increasingly becoming more common in the HAART era compared with the pre-HAART era. Close monitoring and screening for these secondary cancers is desirable in patients with KS.

Disparities in Kaposi sarcoma incidence and survival in the United States: 2000-2013.

ObjectiveGeographic and racial disparities may contribute to variation in the incidence and outcomes of HIV-associated cancers in the United States.MethodUsing the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed Kaposi sarcoma (KS) incidence and survival by race and geographic region during the combined antiretroviral therapy era. Reported cases of KS in men from 2000 to 2013 were obtained from 17 SEER cancer registries. Overall and age-standardized KS incidence rates were calculated and stratified by race and geographic region. We evaluated incidence trends using joinpoint analyses and calculated adjusted hazard ratios (aHR) for overall and KS-specific mortality using multivariable Cox proportional hazards models.ResultsOf 4,455 KS cases identified in men younger than 55 years (median age 40 years), the annual percent change (APC) for KS incidence significantly decreased for white men between 2001 and 2013 (APC -4.52, p = 0.02). The APC for AA men demonstrated a non-significant decrease from 2000–2013 (APC -1.84, p = 0.09). Among AA men in the South, however, APC has significantly increased between 2000 and 2013 (+3.0, p = 0.03). In addition, compared with white men diagnosed with KS during the same time period, AA men were also more likely to die from all causes and KS cancer-specific causes (aHR 1.52, 95% CI 1.34–1.72, aHR 1.49, 95% CI 1.30–1.72 respectively).ConclusionAlthough overall KS incidence has decreased in the U.S., geographic and racial disparities in KS incidence and survival exist.

High Prevalence of Distinct Human Herpesvirus 8 Contributes to the High Incidence of Non-acquired Immune Deficiency Syndrome-Associated Kaposi's Sarcoma in Isolated Japanese Islands.

Non-acquired immune deficiency syndrome (AIDS) Kaposi's sarcoma (KS) is extremely rare in Japan but highly endemic in Okinawa, especially in Miyako Islands. We aimed to elucidate the exact incidence and cause of this high prevalence. Non-AIDS KS cases in Okinawa Prefecture over the past 31 years were reviewed, and human herpesvirus 8 (HHV8) seroprevalence in Miyako Islands was determined. We examined whole-genome sequences of 3 HHV8 strains and performed whole-exome sequencing of 4 male patients from Miyako Islands. Approximately half of the non-AIDS KS cases in Okinawa Prefecture were from Miyako Islands. The age-adjusted incidence rate was 0.87/105 per year for Miyako Islands and 0.056/105 per year for the rest of Okinawa. Human herpesvirus 8 seroprevalence was 15.4% in Miyako Islands. The 3 HHV8 genomes isolated from Miyako islanders formed a phylogenetically branch distinct from those of previously sequenced HHV8 strains and shared specific mutations in 9 proteins. These mutations were verified in Okinawan patients other than those from Miyako Islands. Whole-exome sequencing of the 4 male Miyako Islanders did not reveal shared pathogenic mutations. Miyako Islands are an endemic area of non-AIDS KS. The high rate of a distinct HHV8 may contribute to the high incidence of KS in the region.

Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study.

We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). We included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by ≥95% in other regions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa.

MTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma

Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates, and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (N=274), most (90%) associated with human immunodeficiency virus. Tissue microarray slides were stained with human herpes virus-8, Friend leukemia integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF receptor-β, VEGF, and phospho-mTOR. Both intensity and extent of staining were scored. Multiplying these scores for each core yielded total staining H-scores. Human herpes virus-8 was positive in 87% and Friend leukemia integration 1 transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+ (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were phospho-mTOR+. There was no significant difference in staining among patients with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated the highest proportion of strong positivity (67.1%). These results support the possibility of using targeted inhibitors in KS. Overexpression was independent of CD4 count, suggesting that even patients with low counts may be targeted therapy candidates.

Diagnosis and Treatment of Kaposi Sarcoma.

Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy. Standard KS therapy has not changed in 20 years, but newer modalities are on the horizon and will be discussed.

BALB/c mice immunized with a combination of virus-like particles incorporating Kaposi sarcoma-associated herpesvirus (KSHV) envelope glycoproteins gpK8.1, gB, and gH/gL induced comparable serum neutralizing antibody activity to UV-inactivated KSHV

Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring in Africa, where the virus is endemic. To date, there is no prophylactic vaccine against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus entry into host cells, are attractive vaccine targets for eliciting potent neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1, gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized these VLPs for their composition, size, and functionality. To determine which viral glycoprotein(s) elicit the most effective serum-nAbs, we immunized BALB/c mice with gpK8.1, gB, or gH/gL VLPs individually or in combination. Neutralizing antibody assay revealed that sera from mice immunized with the VLPs inhibited KSHV infection of HEK-293 cells in a dose-dependent manner. As a single immunogen, gpK8.1 VLPs stimulated comparable nAb activity to that of UV-inactivated KSHV (UV-KSHV). In contrast, UV-KSHV stimulated higher titers of nAb compared to gB (p = 0.0316) or gH/gL (p = 0.0486). Mice immunized with the combination of gB and gH/gL VLPs had a better nAb response than those immunized with either gB (p = 0.0268), or gH/gL (p = 0.0397) as single VLP immunogens. Immunization with any VLP combination stimulated comparable nAb activity to UV-KSHV serum. Our data provide the first evidence that KSHV gpK8.1, gB, and gH/gL glycoproteins can be incorporated onto the surface of VLPs and used as prophylactic vaccine candidates, with potential to prevent KSHV infection.

Pulmonary Kaposi Sarcoma with Osseous Metastases in an Human Immunodeficiency Virus (HIV) Patient: A Remarkable Response to Highly Active Antiretroviral Therapy

Patient: Male, 34Final Diagnosis: Pulmonary Kaposi’s sarcoma with bony metastatsesSymptoms: Cough • weight lossMedication: —Clinical Procedure: —Specialty: Infectious DiseasesObjective:Rare diseaseBackground:Kaposi sarcoma (KS) is known to involve the mucocutaneous tissues and the aero-digestive tracts. In acquired immune deficiency syndrome (AIDS) patients, KS has an aggressive course and carries poor prognosis. We present a case of pulmonary KS with osseous metastases as the first presentation of human immunodeficiency virus (HIV) infection in a young male. The lesions impressively decreased in size and numbers following initiation of highly active antiretroviral therapy (HAART).Case Report:A 34-year-old heterosexual male presented with a one month history of cough and 15–20 pound weight loss within six months. Examination revealed oral thrush, decreased breath sounds and crackles on the right lower lung base. Imaging showed a large right perihilar mass with multiple lytic lesions involving thoracic and lumber vertebrae, ribs, sternum, and clavicles. Blood and sputum cultures, smears for acid fast bacilli, and a QUANTIferon gold test were all negative. He tested positive for HIV and his CD4 count was 7 cells/uL. Bronchoscopy with biopsy was unrevealing. Pathology of the right hilar mass was diagnostic of KS. Following initiation of antiretroviral therapy his condition dramatically improved; repeat chest CT scan showed marked regression of the bony and pulmonary lesions.Conclusions:The dual action of HAART on the recovery of the immune system and against human herpes virus 8 (HHV-8) may essentially cause regression of KS lesions.

Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at the University Teaching Hospital, Lusaka, Zambia.

IntroductionHuman herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its causative agent, Human Herpes virus 8 is not sought. This means poor prognosis for affected patients since the causative agent is not targeted during diagnosis and KS lesions may be mistaken for other reactive and neoplastic vascular proliferations when only histological techniques are used. Therefore, this study was aimed at providing evidence of Human Herpes virus 8 infection in Kaposi's sarcoma tissues at the University Teaching Hospital in Lusaka, Zambia.MethodsOne hundred and twenty suspected Kaposi's sarcoma archival formalin-fixed paraffin-wax embedded tissues stored from January 2013 to December 2014 in the Histopathology Laboratory at the University Teaching Hospital, Lusaka, Zambia were analysed using histology and Polymerase Chain Reaction targeting the ORF26 gene of Human Herpes virus 8.ResultsThe predominant histological type of Kaposi's sarcoma detected was the Nodular type (60.7%) followed by the plaque type (22.6%) and patch type (16.7%). The nodular lesion was identified mostly in males (40.5%, 34/84) than females (20.2%, 17/84) (p=0.041). Human Herpes virus 8 DNA was detected in 53.6% (45/84) and mostly in the nodular KS lesions (60%, 27/84) (p=0.035).ConclusionThe findings in this study show that the Human Herpes virus-8 is detectable in Kaposi's sarcoma tissues, and, as previously reported in other settings, is closely associated with Kaposi's sarcoma. The study has provided important baseline data for use in the diagnosis of this disease and the identification of the virus in the tissues will aid in targeted therapy.

Kaposi's sarcoma concealed by stasis dermatitis in a patient with psoriasis.

Kaposi's sarcoma (KS) is a multifocal and angioproliferative neoplasm. KS may be accompanied by psoriasis; however, in most of these cases the main mechanism involves iatrogenic KS associated with the immunosuppressive drugs that are used in psoriasis treatment. In angioproliferative lesions as a result of venous insufficiency and stasis dermatitis, acroangiodermatitis (pseudo-KS) is initially considered. However, the concurrent occurrence of psoriasis, stasis dermatitis, and KS has not been previously reported. We report a case of classic-type KS in an 83-year-old man that was concealed by stasis dermatitis and accompanied by psoriasis.

Imaging Findings in AIDS-related Oral Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is one of the most common diseases in patients with acquired immunodeficiency syndrome, but is rarely encountered in dental practice in Japan. We encountered a case of oral KS (OKS) presenting in the hard palate, gingiva, and tongue in a 41-year-old man. We report the results of imaging, including computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT in this case. The process leading to an imaging diagnosis of OKS is discussed, emphasizing the importance of collating clinical, laboratory, pathological, and radiological findings. The present results suggest that mapping of accurate tumors is very important in cases of OKS, and that multiple or bilateral manifestations, ill-defined margins, osteolysis, and swollen lymph nodes, in particular, need to be taken into account.

A Case of Kaposi's Sarcoma of the Rectum in a Homosexual Male with HIV–AIDS

Kaposi sarcoma (KS) is a locally aggressive endothelial tumor, commonly diagnosed among individuals with acquired immunodeficiency syndrome (AIDS). The most typical site of involvement by KS is the skin, but in some cases, it can also affect other tissues and organs. Most patients with gastrointestinal involvement of Kaposi's sarcoma remain asymptomatic and they are often diagnosed on endoscopy or autopsy. However, there are cases of KS mimicking ulcerative colitis (UC), whereby clinical manifestations can confuse physicians. We report a 31 y old homosexual man who presented with rectal pain and bleeding. Patient was diagnosed eight years ago with HIV/ AIDS, and despite highly active retroviral therapy, he developed extensive skin lesions. Because of expressive rectal pain and bleeding, he underwent rectoscopy, which revealed ulcerous and hemorrhagic lesions. The rectoscopic and clinical presentation mimicked acute flare of UC, which was patient initial diagnosis. Tissue samples were collected for microscopical examination. After histological, histochemical and immunhistochemical examination of the sampled tissue, KS diagnosis was confirmed. The clinical manifestations of Kaposi sarcoma can be confused with acute exacerbation of ulcerative colitis often delaying the diagnosis. Therefore, early endoscopic evaluation with adequate biopsies could help in timely diagnosis and management of gastrointestinal KS (GI-KS) in patients with HIV/AIDS, even if they do not have skin lesions.

Lymphadenopathic kaposi sarcoma in an immunocompetent young patient: a case report

Kaposi's sarcoma (KS) is a vascular lesion that usually originates from several sites in the mid-dermis extending into the dermis. Infection from human herpes virus type 8 (HHV-8) is the mostly associated cause. Several articles reported cases of KS, first in Africa, then worldwide because of its close association with HIV / AIDS. KS may also be due to iatrogenic immunosuppression of chronic steroid use, high level of expression of many cytokines and angiogenic growth factors. It can involve skin, mucous membranes, lymph nodes and viscera. We report a case of a 24-year-old immunocompetent, HIV negative male who presented with indolent lymphadenopathy, after adenectomy and histological and immunohistochemical examination revealed a KS. The patient did not have skin lesions. Refusing any other therapy, our patient still lives healthy.This very rare case shows that KS does not always equal immunodeficiency.

HIVNegative Disseminated Cutaneous Kaposi’s Sarcoma: Three Case Reports.

Kaposi’s sarcoma (KS) is a malignant disease that originates from the vascular endothelium and has a very variable clinical course. Classic KS is usually limited the lower extremities and runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesion; whereas immunodeficiency-related diseases frequently disseminate and involve several organs. Here, we presented three HIV-negative disseminated cutaneous KS cases with different clinical presentations and coexistent diseases.

Classic Kaposi sarcoma in an HIV-negative Han Chinese man: a case report

Kaposi sarcoma (KS) is a multifocal angioproliferativetumor of endothelial origin. Despite nearly identicalclinical and histopathologic presentations, KS isclassified into four distinct varieties: classic/sporadic,AIDS-associated, African/endemic, and iatrogenic. Allsubtypes are invariably linked to human herpesvirus-8(HHV-8) and show a male predilection. Classic Kaposisarcoma is exceedingly rare in the Asian populationand its incidence varies by region and ethnic grouppredominance. A study in the Xinjiang region of Chinafound that only 1% of classic KS cases occurred inpatients belonging to the Han Chinese ethnic group,which formulates 84% of the Taiwanese population.Therefore, classic KS is extremely rare in Taiwan, withvery few reports describing the manifestations ofdisease in this population. We report a case of animmunocompetent 68-year-old HIV-negative HanChinese man born and raised in Taiwan with classicKaposi sarcoma on his trunk and extremities.

Ultraviolet Radiation and Kaposi Sarcoma Incidence in a Nationwide US Cohort of HIV-Infected Men.

Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression. All statistical tests were two-sided. Based on discharge records, there were 422 newly diagnosed KS cases among 17 597 HIV-infected veterans. Cohort members with prior NMSC had a statistically significantly increased risk of KS (HR = 8.64, 95% CI = 6.23 to 11.96) in the total population. Risk of KS was higher for quartile 4 vs 1 among the total population (HR = 1.49, 95% CI = 1.02 to 2.16, Ptrend UVR quartile [coded 1 to 4] = .02) and among whites (HR = 1.75, 95% CI = 1.11 to 2.78, Ptrend = .009), but not among African Americans (HR = 1.23, 95% CI = 0.71 to 2.15, Ptrend = .23). KS risk was elevated among HIV-infected men with NMSC diagnosis and in those living in locations with high ambient UVR at time of HIV diagnosis. Our novel findings suggesting that UVR exposure may increase KS risk warrant further investigation.

A Rare Case Report of Hepatic Kaposi Sarcoma

Kaposi sarcoma (KS) is the most frequent opportunist neoplasm found in AIDS patients. Hepatic involvement is rarely diagnosed at life. We report a case of biopsy proven hepatic KS in a patient with AIDS. A 34-year-old African American male with past medical history of HIV, not on HAART therapy for last 2 years and with no prior history of liver disease who presented with complaints of fatigue, fever, night sweats and sorethroat. On physical examination he had multiple hyperpigmented skin lesions in the temporal and maxillary regions, oral thrush and hepatomegaly. His Alkaline phosphatase 328 mu/ml, ALT 26 mu/ml, AST 50 mu/ml, Total bilirubin 1.9 mg/dl, platelets 62X10E9 and INR 1.23. His CD4 count was found to be 14 cells/μL. Abdominal ultrasound showed heterogeneous liver and CT abdomen showed characteristic multiple hypo dense lesions that were suggestive of hepatic KS. The patient underwent skin and liver biopsy which confirmed the diagnosis of KS. Liver biopsy showed portal areas that were expanded by an atypical spindle cell proliferation forming slit-like spaces and cells were positive for HHV-8. The patient was started on antiretroviral therapy and initiation of chemotherapy. AIDS-related Kaposi sarcoma is most often multicentric, extensive and aggressive. While KS can be seen at any stage of HIV infection, advanced disease with multifocal involvement usually occurs with a CD4 count < 200 cells/ μL. Hepatic involvement is unusual and asymptomatic. Ultrasonography shows echogenic infiltration and heterogeneous parenchyma with small hyperechoic nodules. CT shows hypodense lesions. In a patient with cutaneous or digestive Kaposi sarcoma lesions, these radiological aspects are suggestive of hepatic involvement. However, a definitive diagnosis of KS requires biopsy and histological examination. Treatment with chemotherapy is usually indicated because of the rapid progression of the tumor, although no prolongation of survival has been demonstrated. Hepatic KS is rarely reported in living patients. Autopsies show liver involvement in 35% of patients with KS. When characteristic radiological findings are encountered in an HIV-positive patient liver biopsy should be performed to clinch the diagnosis.Figure 1Figure 2

Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy: Collaborative Analysis of 21 European Cohort Studies.

Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European observational HIV cohorts. We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models. We included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted for exposure group, origin, age, type of first-line regimen, and calendar year, low current CD4 cell counts increased the risk of developing KS throughout all observation periods after cART initiation. Lack of viral control was not associated with the hazard of developing KS in the first year after cART initiation, but was over time since starting cART increasingly positively associated (P < .001 for interaction). In patients initiating cART, both incidence and risk factors for KS change with time since starting cART. Whereas soon after starting cART low CD4 cell count is the dominant risk factor, detectable HIV-1 RNA viral load becomes an increasingly important risk factor in patients who started cART several years earlier, independently of immunodeficiency.

Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma.

Backgroundc-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter.ObjectiveTo investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV.MethodsA total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked.ResultsAlthough c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001).Conclusionc-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.

Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.

Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n=20) with the control group comprising inflamed MC (n=20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100%). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.