Sarcoma de Kaposi en personas que viven con VIH-SIDA en un hospital público de referencia en Perú / Kaposi's sarcoma in people living with HIV/aids in a public referral hospital in Peru

RESUMEN El sarcoma de Kaposi (SK) es el cáncer más frecuente en las personas que viven con VIH. Las investigaciones sobre esta condición son escasas en la región, por lo que, el objetivo de este artículo fue describir las características demográficas, clínicas y terapéuticas de los pacientes con VIH que desarrollaron SK en el Hospital Cayetano Heredia entre el 2000 y 2018. Se identificaron 129 casos de SK, con una mediana de edad de 33 años, con predominio en varones con el 92% (119/129), y en su mayoría hombres que tienen sexo con hombres (HSH). La mediana de tiempo desde el diagnóstico de VIH hasta el del SK fue de cinco meses, asociado con un recuento de linfocitos CD4 de 64 células/µL (RIC: 33-185) al momento del diagnóstico de SK. El compromiso cutáneo fue el más común; sin embargo, al menos la mitad de ellos también tuvo la forma visceral.

ABSTRACT 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.

Angiosarcoma in HIV-negative patients is not associated with HHV-8

Abstract: BACKGROUND: Angiosarcoma is an aggressive, malignant neoplasm of vascular or lymphatic origin. Herpes virus 8 (HHV-8) is a member of the herpes family with a tropism for endothelial cells and it has been proven to induce vascular neoplasms, such as Kaposi's sarcoma. The role of HHV-8 in the pathogenesis of angiosarcoma has not been well defined. OBJECTIVE: To investigate the relationship between the presence of HHV-8 and angiosarcoma. METHODS: In this study, the team investigated the relationship between the presence of HHV-8, as determined by polymerase chain reaction, and angiosarcoma, using samples from patients with epidemic Kaposi's sarcoma as controls. RESULTS: While all control cases with epidemic Kaposi's sarcoma were positive for HHV-8, none of the angiosarcoma cases was. CONCLUSION: These findings support most previous studies that found no association between HHV-8 and angiosarcoma.

Mycosis fungoides and Kaposi's sarcoma association in an HIV-negative patient

Abstract The association of mycosis fungoides and kaposi’s sarcoma in HIV-negative patients is a rare phenomenon. The presence of human herpesvirus 8 (HHV-8) – associated with all forms of Kaposi’s sarcoma – has also been recently identified in mycosis fungoides lesions. However, a causal association between HHV-8 and the onset of mycosis fungoides has not been established yet. The present case reports a patient who developed Kaposi’s sarcoma lesions after a two-year UVB phototherapy to treat a mycosis fungoides. Negative immunohistochemistry staining for Kaposi’s sarcoma-associated herpesvirus in the initial mycosis fungoides lesions strengthens the absence of a link between Kaposi’s sarcoma-associated herpesvirus and mycosis fungoides. Immunosuppression caused by the lymphoma and prolonged phototherapy were probably the contribut ing factors for the onset of Kaposi’s sarcoma.

Lesiones orales asociadas con la enfermedad del virus de inmunodeficiencia humana en pacientes adultos, una perspectiva clínica / Oral lesions associated with human immunodeficiency virus disease in adult patients, a clinical perspective

Among the clinical manifestations which may occur in HIV/AIDS patients, oral lesions are relevant because there are easily accessible and usually the diagnosis is made through clinical features. Some oral manifestations are strongly related with HIV/AIDS patients indicating infection and progression to AIDS and also allow monitoring the success or failure of using antiretroviral therapy. The massive introduction of antiretroviral therapy has changed the morbidity and mortality, frequency, type of clinical manifestation and the timing of the classic opportunistic complications. The aim of this review is to provide an updated of the classical clinical features of the most frequent and relevant HIV/AIDS oral manifestations, considering the fundamental clinical features for their diagnosis.

Dentro de las manifestaciones que pueden aparecer en los pacientes con infección por VIH/SIDA, las lesiones de la cavidad oral tienen gran relevancia debido a que son fácilmente accesibles y por lo general su diagnóstico se efectúa a través de signos clínicos. Además, algunas manifestaciones orales están fuertemente relacionadas con el síndrome por lo que indican sospecha de infección y progresión a etapa SIDA y permiten monitorizar el éxito o fracaso de la terapia anti-retroviral empleada. La introducción masiva de la terapia anti-retroviral ha modificado la morbi-mortalidad, la frecuencia, el tipo de manifestación clínica y el momento de aparición de las clásicas complicaciones oportunistas. El objetivo de esta revisión es entregar las características clínicas clásicas actualizadas de aquellas manifestaciones orales asociadas a la infección por VIH/SIDA que son más frecuentes y que tienen mayor relevancia clínica, considerando las características fundamentales para su diagnóstico.

Sarcoma de Kaposi por virus del herpes humano de tipo 8 en un receptor de trasplante hepático pediátrico: Caso clínico / Human herpesvirus 8 related Kaposi's sarcoma in a pediatric liver transplant recipient: Case report

Los pacientes que reciben tratamiento inmunosupresor están en riesgo de desarrollar tumores malignos. La infección primaria o reactivación del virus del herpes humano de tipo 8 (HHV-8) puede predisponer al sarcoma de Kaposi después del trasplante de un órgano sólido. En los receptores de trasplantes pediátricos, este sarcoma tiene baja incidencia y mal pronóstico. Se informa la presentación clínica de un sarcoma de Kaposi en un ganglio linfático luego de una infección por HHV-8 en un niño a los 4 meses del trasplante hepático. El paciente tuvo buena evolución con suspensión del tacrolimus y conversión a sirolimus un mes después del diagnóstico. En nuestro conocimiento, este es el primer caso de sarcoma de Kaposi en un receptor pediátrico de trasplante hepático informado en nuestro país y creemos que esta entidad debería considerarse como diagnóstico diferencial en las complicaciones postrasplante.

Patients under immunosuppressive treatment are at risk of developing malignant tumors. Primary infection or reactivation of human herpesvirus 8 (HHV-8) may predispose to Kaposi's sarcoma (KS) after solid organ transplantation. KS in pediatric liver transplant recipients has low incidence and poor prognosis. We report the clinical presentation of a KS in lymph node following HHV-8 infection in a pediatric patient presenting four months after liver transplantation. He had a good outcome with suspension of tacrolimus and conversion to sirolimus one month after diagnosis. To our knowledge, this is the frst KS reported case in our country after liver transplant in a pediatric recipient and we believe that this entity should be taken into consideration in the differential diagnosis of post-transplant complications.

Virus como inductores de neoplasias cutáneas / Viruses as agents inducing cutaneous neoplasms

El rol oncogénico de los virus en las neoplasias cutáneas es conocido por el hombre desde hace más de un siglo, cuando se atribuía el origen de la verruga vulgar al virus papiloma humano (VPH). En la actualidad, las neoplasias inducidas por virus pueden agruparse en tumores sólidos y procesos linfoproliferativos. Destacan entre los primeros el VPH, del cual ahora conocemos numerosos serotipos, cada uno vinculado a una neoplasia específica, el herpesvirus humano tipo 8 que produce el sarcoma de Kaposi y el poliomavirus vinculado al carcinoma de Merkel. Entre los procesos linfoproliferativos debemos mencionar al virus linfotrópico de células T humanas tipo 1 (HTLV-1) responsable de los linfomas de células T, en los cuales el compromiso cutáneo es inespecífico, con un amplio espectro de presentaciones clínicas y, que por consiguiente, plantean un reto para el diagnóstico diferencial. En este grupo también se encuentra el virus Epstein Barr vinculado a los linfomas nasales de Células NK/T y a los linfomas tipo Hidroa, de reciente descripción. En esta era en la que lo genético y lo molecular priman en las investigaciones en cáncer, no podemos dejar de lado el concepto de neoplasia como resultado de la infección por un agente viral, lo que abre una nueva veta de posibilidades de tratamiento anticanceroso basado en medicamentos antivirales.

The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.

Multi-transmembrane protein K15 of Kaposi's sarcoma-associated herpesvirus targets Lyn kinase in the membrane raft and induces NFAT/AP1 activities

Viral proteins of gamma-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi's sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization. However, the detailed mechanism underlying this phenomenon was not understood. In the C-terminal cytoplasmic region of K15, putative binding domains for Src-SH2 and -SH3 were identified. In this study, we attempted to characterize these modular elements and cellular binding protein(s) by GST pull down and co-immunoprecipitation assays. These studies revealed that K15 interacted with the major B cell tyrosine kinase Lyn. In vitro kinase and transient co-expression assays showed that the expression of K15 protein resulted in activation of Lyn kinase activity. In addition, GST pull down assay suggested that the SH2 domain of Lyn alone was necessary for interaction with the C-terminal SH2B (YEEV) of K15, but the addition of Lyn SH3 to the SH2 domain increases the binding affinity to K15 protein. The data from luciferase assays indicate that K15 expression in BJAB cells induced NFAT and AP1 activities. The tyrosine residue in the C-terminal end of K15 required for the Lyn interaction appeared to be essential for NFAT/AP1 activation, highlighting the significance of the C-terminal SH2B of K15 as a modular element in interfering with B lymphocyte signaling through interaction with Lyn kinase.

Detection of human herpes virus-8 in kaposi sarcoma and other vascular tumors; immunohistochemical analysis

The diagnostic distinction of some vascular tumors and Kaposi's sarcoma [KS] can be sometime difficult. Recently, a monoclonal antibody to human herpes virus- 8 latent nuclear antigen-1 has been demonstrated in Kaposi's sarcoma. In this study the usefulness of this antibody is evaluated to differentiate Kaposi's sarcoma from the other vascular lesions. Formalin-fixed, paraffin-embedded tissue sections [4 micro m] from 20 cases of Kaposi sarcoma, ten cases of capillary hemangioma [pyogenic granuloma], five cases of angiosarcoma, three cases of hemangioendothelioma, three cases of vascular transformation of lymph nodes were examined immunohistochemically for HHV-8 using mouse monoclonal antibody [NCL-HHV8-LNA], Novocastra, United Kingdom. It is specific for human herpesvirus type 8 latent nuclear antigen-1 [LNA-1]. Nuclear staining in tumor cells was considered a positive result. HHV-8 stain showed strong, diffuse, nuclear staining for human herpes virus 8 latent nuclear antigen-1 in all, 20/20 cases of Kaposi sarcoma [100%], whereas all cases of hemangioma, angiosarcoma, hemangioendothelioma and vascular transformation of lymph nodes were negative for this antigen. Immunohistochemistry for HHV-8 is a characteristic immunohistochemical marker of Kaposi sarcoma and considered as a very useful tool for differentiation between Kaposi sarcoma and other vascular lesions

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

Kaposi's sarcoma (KS) became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS) in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100 percent. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2 percent) cases of classical KS, 29 (56.9 percent) of AIDS-associated KS and 2 (3.9 percent) of iatrogenic KS. Most patients were males (7.5:1, M/F), and mean age was 47.9 years (SD = ± 18.7 years). As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque) compared to classical KS patients (predominantly nodular lesions). This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1 percent), irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

Sarcoma de Kaposi en inmunosuprimido iatrogénico: reporte de un caso / Iatrogenic Kaposi's sarcoma in patients undergoing immunosuppresive therapy: a case report

El Sarcoma de Kaposi es una neoplasia de origen vascular que presenta cuatro formas clínicas: en ancianos de origen mediterráneo, en adultos y adolescentes en Africa, asociado a SIDA y en forma iatrogénica en pacientes inmunosuprimidos tanto por trasplante como por enfermedades autoinmunes o inflamatorias. En todos los casos se ha propuesto una relación etiológica con el virus herpes humano tipo 8; sin embargo, ésta es una condición necesaria pero no suficiente para desarrollar el tumor. En este sentido se ha planteado un posible rol directo de los corticoides como inmunosupresores. Presentamos un caso de sarcoma de Kaposi en una mujer mayor en tratamiento prolongado con corticoides y una revisión de la literatura.

Kaposi 's sarcoma herpes virus: diagnosis, epidemiology and clinical significance with special reference to the situation in Saudi Arabia

Human herpes virus 8 [HHV-8], which is as yet the single known human gamma herpes virus, is also known as Kaposi's sarcoma herpes virus [KSHV] because of its strong association with the tumor. The present study is aimed to contribute to the awareness of existence of HHV-8 in Saudi Arabia and its clinical implications especially with regard to the associated risk of developing Kaposi's sarcoma in immuno-compromised patients. This article review recent research findings on various aspects of HHV-8 including epidemiology and clinical importance, and discusses serology testing for the virus and prospects of antiviral therapy. The paper also discusses recent findings on prevalence of HHV-8 in renal transplant recipients with special reference to patients from Saudi Arabia. HHV-8 does not seem to be widespread in the general population of Saudi Arabia. The increased HHV-8 antibody prevalence in renal transplant recipients in the country is partially explained by the induced immune suppression. Running Title: Kaposi's sarcoma herpes virus and clinical significance

HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8) in HIV-positive Brazilian patients with (HIV+/KS+) and without Kaposi's sarcoma (HIV+/KS-) using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA) antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3 percent of KS+ patients and in 3.7 percent of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5 percent) and KS- patients (18.5 percent). HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR) = 7.4, 95 percent confidence interval (CI) = 2.16-25.61) or anti-LNA and anti-lytic antibodies (OR = 17.0, 95 percentCI = 4.91-59.14). Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02), but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging

Kaposi's sarcoma occurring during short-term dialysis: report of two cases

Kaposi's sarcoma (KS) appears to develop in association with kidney transplantation, but unlikely with dialysis. We report two cases of classic KS that occurred in patients receiving short-term (less than 3 yr) dialysis. They have been suffering from chronic renal failure due to tuberculosis and diabetes mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques and nodules were found on the hand and the lower extremities. Laboratory studies showed no evidence suggesting immunosuppressed state and there was no history of taking immunosuppressive agents. The biopsies of the two cases revealed proliferation of spindle-shaped cells focally arranged in bundles and multiple dilated vascular spaces outlined by an attenuated endothelium with intravascular and extravasated erythrocytes. The specimens expressed positivity with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was detected in one case by polymerase chain reaction method.

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula

Sarcoma de Kaposi: a propósito de una revisión clinicopatológica / Kaposi's sarcoma: a propose of a clinic-pathological review

Desde la aparición de la enfermedad del Sida, se ha profundizado el estudio sobre sarcoma de kaposi (SK) debido a la asociación de esta neoplasia con la infección por el virus VIH. Sin embargo, debe recordarse que existen también otras formas de sarcoma de kaposi no asociadas al Sida. Ultimamente se ha investigado la patogenia del SK y se han postulado varias teorías que explicarían el origen de esta enfermedad. En el presente trabajo, se analizan las características clínicas, histológicas, junto a la etiología de esta neoplasia, así como su tratamiento; además, se incluye el análisis del diagnóstico histológico realizado de los casos biopsiados en nuestro Departamento desde 1979 a 1994