Human herpes virus-8-negative kaposiform sarcoma in a HIV-positive male: Novel variant

Human herpes virus (HHV)-8 is associated with causation of Kaposi's sarcoma (KS). An HIV-positive male with multiple nodules on the body was clinically and histopathologically diagnosed as a case of KS; however, immunohistochemistry was negative for HHV-8. This peculiar scenario of HHV-8-negative tumor with typical clinical and histopathologic findings was labeled as “Atypical spindled endothelial proliferation suspicious of Kaposi sarcoma”, hitherto unreported novel entity

Diagnosis of elephantiasis nostras verrucosa as a clinical mani-festation of Kaposi's sarcoma / Diagnóstico de elefantiasis nostras verrucosa como mani-festación clínica del Sarcoma de Kaposi

Elephantiasis nostras verrucosa, a rare manifestation of Kaposi's sarcoma, is a progressive cutaneous hypertrophy caused by chronic non-filarial lymphedema secondary to obstruction of the lymphatic system that can lead to severe disfigurement of parts of the body that have gravity-dependent blood flow, due to edema, fibrosis, and hyperkeratosis, especially lower extremities. Among the various conditions that can induce chronic lymphedema are tumors, trauma, radiotherapy, obesity, hypothyroidism, chronic venous stasis, and AIDS-related Kaposi's sarcoma. Kaposi's sarcoma is a vascular tumor associated with the presence of human gammaherpesvirus 8 that is predominantly cutaneous, locally aggressive, with metastasis, and is associated with the production of factors that favor inflammation, lymphatic obstruction, and lymphedema.

Sarcoma de kaposi en pacientes vih: a proposito de dos casos / Kaposi´s sarcoma in hiv patients: regarding two case report

RESUMEN: El Sarcoma de Kaposi es unaneoplasia de origen vascular,asociado obligadamente al virus Herpes Humano tipo 8. Presenta manifestaciones cutáneas en primer lugar, mucosas, ganglionares y viscerales. Puede evolucionar de forma leve con lesiones cutáneas, hasta casos fulminantes con compromiso sistémico, en caso de no realizar tratamiento. Existen múltiples opciones terapéuticas, las cuales se definen según el compromiso de la enfermedad y la afectación del paciente por su patología de base.El diagnóstico se basa en la sospecha clínica y se confirma con una biopsia histopatológica. El sarcoma de Kaposi corresponde a la neoplasia más frecuente en los pacientes con VIHse encuentraprincipalmente en hombres homosexuales. En este artículo se presentan dos pacientes con VIH con diagnóstico de Sarcoma de Kaposi y se realiza una breve revisión de la bibliografía.

ABSTRACT: Kaposi´s sarcoma is a vascular origin neoplasm, obligatory associated with Human Herpes Virus 8. It presents cutaneous manifestations at a first place, mucous, ganglionic and viscerals. It may present a mild presentation with cutaneous manifestations, up to fulminant cases with systemicinvolvement,in case of not being treated. There are a number of therapeutic options, defined by the state of the illness and the involvement of the patient due to the primary pathology. The diagnosis is based on the clinical suspicion and it is confirmed by a histopathological biopsy. Kaposi´s sarcomais the most frequent neoplasm in patients with HIV, being more frequently in homosexual men. In this article two HIV patients with Kaposi´s sarcoma diagnosis are exposed and a brief revision of the literature is done.

Eyelid Kaposi Sarcoma in an HIV-negative Patient

Kaposi sarcoma (KS) is a low-grade, multicentric vascular neoplasm. Most commonly, it involves the skin, but it can occur at any site on the body. The cutaneous lesions are often located on the lower legs, genitalia, oral mucosa, and face. KS is categorized in four different types: classic, endemic, epidemic or AIDS associated, and transplantation associated. We report a case of HIV-negative, classic KS located on the eyelid. The eyelid lesion was completely excised, and after a 1-year follow-up, no recurrences were observed. Ocular involvement by KS in a patient who is serologically negative for HIV is extremely rare.

Treatment of multicentric castleman’s disease: Research advances / 国际药学研究杂志

Castleman’s disease (CD) is a rare lymphoproliferative disorder which comprises two distinct clinical subtypes: unicentric CD (UCD) and multicentric CD (MCD). Unlike UCD, which is a curable disease with surgical resection, MCD is a disease with systemic symptoms and high mortality rate (the 5-year mortality rate could be as high as 35%). There is no standard of care for MCD. Current treatment options include observation, glucocorticoids, chemotherapy (with or without rituximab) and immunomodulatory agents. Progress have been made during the recent years, interleukin-6 (IL-6) and human herpes virus 8 (HHV-8) have been recognized as key factors involved in the pathogenesis of MCD. Accordingly, drugs targeting these factors (especially IL-6) have been developed to treat MCD. In this paper, we try to review the current treatment options and new emerging therapies for MCD which might help Chinese clinicians to learn more about this rare disease.

Mucocutaneous Kaposi's sarcoma in an HIV-positive patient: diagnosis and treatment / Sarcoma de Kaposi mucocutâneo em paciente HIV positivo: diagnóstico e tratamento

ABSTRACT Kaposi's sarcoma (KS) is an endothelial neoplasia caused by infection with the human herpesvirus 8 (HHV-8), and the type associated with the human immunodeficiency virus (HIV) is considered the most aggressive and frequent. This paper reports a case of mucocutaneous KS in a patient not formerly aware of being an HIV bearer. A 38-year-old male patient has sought treatment with multiple oral lesions and one in the skin. Serology was positive for HIV and incisional biopsy diagnosed KS. After 11 months of chemotherapy and antiretroviral therapy, there was complete remission of the skin KS and partial remission of oral lesions.

RESUMO Sarcoma de Kaposi (SK) é uma neoplasia endotelial causada pelo herpes vírus humano tipo 8 (HHV-8), e o tipo associado ao vírus da imunodeficiência humana (HIV) é considerado o mais agressivo e frequente. Relata-se um caso de SK mucocutâneo em indivíduo não anteriormente ciente de ser portador de HIV. Paciente do sexo masculino, 38 anos, procurou atendimento com queixa de múltiplas lesões orais e uma lesão em pele. A sorologia foi positiva para HIV, e a biópsia incisional das lesões teve como diagnóstico SK. Após 11 meses de terapia antirretroviral e quimioterapia, houve remissão completa do SK cutâneo e parcial das lesões orais.

Extracavitary primary effusion lymphoma: A case report from India.

We present a case of extracavitary primary effusion lymphoma presenting, as jejunal polyps in a 38-year-old man. This is the first report of this entity from India. Although rare in our country, the diagnosis should be suspected in cases of CD20 negative large cell lymphoma with plasmablastic or immunoblastic differentiation in seropositive patients. Immunostaining for latency-associated nuclear antigen-1 and in situ hybridization for Epstein-Barr virus-associated RNA will confirm the diagnosis.

Seroprevalence of Human Herpes Virus 8 among Blood Donors in National Blood Centre, Kuala Lumpur, Malaysia.

Aims: In South East Asia, there is no regional or local HHV-8 seroprevalence data on blood donors. Thus this study was aimed to determine the seroprevalence of HHV-8 among blood donors in National Blood Centre, Kuala Lumpur (NBCKL) and to test its association with donor socio demographic and transfusion transmitted infection (TTI) seropositivity. Study Design: A cross sectional study. Place and Duration of Study: National Blood Centre, Kuala Lumpur (NBCKL). Duration of the study from January 2008 to June 2009. Methodology: A total of 761 serum samples were collected of which 670 from blood donors who were non-reactive for TTIs while 91 were from blood donors who were reactive for TTIs were tested for HHV 8 using BIOTRIN HHV-8IgG EIA kit and BIOTRIN HHV-8IgG Immuno fluorescent assay (IFA). Results: The HHV-8 seroprevalence among blood donors in NBCKL was 1.3% (10/761) of which 0.9% (6/670) among healthy blood donors and 4.4% (4/91) among TTI seropositive donors. TTI seropositivity (p=0.023) and gender (p=0.018) shows a significant risk factors contributed to HHV-8 seropositivity. Human Immunodeficiency Virus (HIV) and Hepatitis C were associated with an increased risk of HHV-8 seropositivity (OR 6.8; 95% CI, 0 to 0.2 and OR 10.0; 95% CI, 0.1 to 0.4 respectively). Conclusion: HHV-8 has a low seroprevalance among blood donors in the NBCKL with a male predominance. A donor with seropositivity for TTI, is associated with a higher risk HHV-8 seropositivity.

Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas

Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B-cell neoplasm that presents as an effusion with no detectable tumor in individuals with human immunodeficiency virus infection or other immune deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic. The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell-associated antigens, and characteristically express lymphocyte activation antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome. Similar conditions associated with HHV8 but not effusion-based are called "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV-positive, body cavity-based lymphomas in patients with long-standing chronic inflammation; the latter can occur in tuberculous pleuritis, artificial pneumothorax, chronic liver disease and various other conditions. Despite their morphological similarity, these various lymphomas require different therapeutic strategies and have different prognostic implications. Correct diagnosis is essential to manage and predict the outcome of patients with PEL and related disorders.

Normalización de un sistema de reacción en cadena de la polimerasa en tiempo real para la cuantificación del herpesvirus humano 8 / Standardization of a real-time polymerase chain reaction system for quantification of human herpesvirus 8

OBJETIVO: normalizar un sistema de reacción en cadena de la polimerasa en tiempo real para determinar la carga viral del herpesvirus humano 8, en diferentes muestras clínicas de pacientes en los que se sospeche la infección por este agente. MÉTODOS: se evaluaron 3 de los métodos reportados internacionalmente para obtener ADN estándar en la construcción de curvas externas estándar, que permiten determinar el número de copias de ADN diana en la muestra problema. RESULTADOS: se obtuvieron 3 ADN estándar a partir del clonaje de un fragmento del gen ORF26 del herpesvirus humano 8 en un vector (ADN plasmídico), con la utilización de productos purificados de reacción en cadena de la polimerasa y el empleo de ADN genómico de la línea celular BCBL. Se pudieron construir las curvas patrón a partir de cada uno de los ADN estándar obtenidos, los que mostraron una fuerte correlación lineal (r= -1) y valores muy bajos de error a lo largo de 6 magnitudes de concentración de ADN diana. El límite inferior de detección a partir del ADN plasmídico y de los productos de reacción en cadena de la polimerasa fue de hasta 100 copias, mientras que con el ADN genómico fue de hasta 10 copias; este último sistema resultó el más sensible. CONCLUSIONES: la reacción en cadena de la polimerasa en tiempo real normalizada a partir de los 3 ADN estándar probó ser un sistema rápido, específico y altamente sensible que permitirá un mejor diagnóstico y además desarrollar estudios sobre la patogenia de la infección por el herpesvirus humano 8 en Cuba.

OBJECTIVE: to standardize a real-time polymerase chain reaction system to determine the human herpes virus 8 viral load in several samples from patients suspected of this type of infection. METHODS: three internationally known methods were evaluated to obtain standard DNA in standard external curve constructions, which allow determining the number of target DNA copies in the suspected samples. RESULTS: three standards DNA were obtained from cloning ORF26 gene fragment of human herpesvirus 8 in a vector (plasmid DNA), with the use of purified polymerase chain reaction products and of genomic DNA of BCBL cell lines. The pattern curves were constructed on the basis of each of the resulting standard DNA, which showed strong linear correlation (r= -1) and very low error values throughout 6 target DNA concentrations. The lower detection limit based on plasmid DNA and the polymerase chain reaction products was 100 copies, whereas that obtained with genomic DNA reached up to 10 copies; this last system turned to be the most susceptible. CONCLUSIONS: real-time polymerase chain reaction system, standardized for the three standard DNA proved to be a rapid, specific and highly sensitive system for better diagnosis, and for the development of studies on the pathogenesis of human herpesvirus 8 infection in Cuba.

Primary Effusion Lymphoma: An Untrivial Differential Diagnosis for Ascites

A primary effusion lymphoma is a rare type of non-Hodgkin's lymphoma where serous cavities are involved. That-cause peritoneal, pleural and pericardial effusions without any lymphadenopathy. They affect immunosuppressive patients with human herpes virus-8 being the suspected etiological agent. The prognosis is usually poor despite treatment. Herein, the case of an immunocompetent patient with ascites and pleural effusion diagnosed as primary effusion lymphoma is presented and discuss the case in the light of the current literature.

A Case of Zosteriform Kaposi's Sarcoma after Prednisolon Treatment / 대한피부과학회지

Kaposi's sarcoma is a rare lympho-angioproliferative neoplasm with four types of variants: classic, iatrogenic immunosuppressive drug-associated, AIDS-related and Africa-endemic Kaposi's sarcoma. Most immunosuppressive drug- associated Kaposi's sarcomas usually occur after a kidney transplant or after receiving immunosuppressive therapy. A 64-year-old female patient showed numerous purpuric nodules and smaller erythematous plaques on the right lower leg for three months. Previously, the patient was treated with an immunosuppressive drug for rapidly progressive glomerulonephritis for a five-week period. A skin biopsy was performed under the clinical diagnosis of Kaposi's sarcoma. We performed immunohistochemical staining and polymerase chain reaction to detect human herpes virus 8 (HHV-8). We report a case of iatrogenic immunosuppressive drug-associated zosteriform Kaposi's sarcoma that rapidly occurred five weeks after prednisolon therapy in a rapidly progressive glomerulonephritis patient.

Complete Remission in a Patient with Human Herpes Virus-8 Negative Multicentric Castleman Disease Using CHOP Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder. Although MCD pathogenesis is unclear, studies have suggested that human herpesvirus 8 (HHV-8) may be associated with the disorder. Recent reports have identified MCD cases without viral infection. A 43-year-old woman presented to our hospital for fever and myalgia of 6 months' duration. The complete blood count revealed an elevated leukocyte count (15.1x10(3)/microliter) and a decreased hemoglobin level of 10.0 g/dL. The C-reactive protein level was elevated at 276.5 mg/L. Thoracic computed tomography (CT) scans revealed bilateral axillary lymphadenopathy. There was no evidence of HHV-8, human immunodeficiency virus (HIV), or Mycobacterium infection. Histologic evaluation of a lymph node biopsy from the left axilla yielded a diagnosis of MCD. Cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) were administered for a total of 4 cycles. The patient's fever and lymphadenopathy resolved after the course of chemotherapy. She has been in complete remission for 24 months at this writing. As previously reported, this case report suggests that MCD can develop without viral infection. CHOP chemotherapy may be an effective treatment option for newly diagnosed MCD patients.

Virus herpes humano 8: detección en células mononucleares de sangre periférica de pacientes con la infección por el virus de inmunodeficiencia humana: con/sin sarcoma de kaposi / Human herpes virus 8: detection in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection with/without kaposi sarcoma

El ácido nucleico proveniente del virus herpes humano 8 esta presente en las células mononucleares de sangre periférica de un 50% a 90% de los pacientes con sarcoma de Kaposi, y 7% a 10% de los pacientes con la infección por el virus de inmunodeficiencia humana sin sarcoma de Kaposi. Nosotros estudiamos la prevalencia del virus herpes humano 8 en células mononucleares de sangre periférica provenientes de pacientes con la infección por el virus inmunodeficiencia humana con/sin sarcoma de Kaposi. Setenta y seis pacientes con la infección por el virus de inmunodeficiencia humana sin sarcoma de Kaposi y 15 pacientes con sarcoma de Kaposi asociado a la infección por el virus de inmunodeficiencia humana se incluyeron en el estudio. El ácido desoxirribonucleico se extrajo utilizando el método de fenol/cloroformo. El ácido desoxirribonucleico fue amplificado a través de la reacción en cadena de la polimerasa utilizando las sondas KS1 y KS2 específicas para el ORF26 del virus herpes humano 8. Las reacciones se consideraron positivas sólo si los productos de la región esperada de 233 pares de bases. Ninguno de los pacientes con la infección por el virus de inmunodeficiencia humana mostró la presencia de virus herpes humano 8 en las células mononucleares de sangre periférica, y después de un seguimiento de 2 años, ninguno ha desarrollado sarcoma de Kaposi. El virus herpes humano 8 se detectó en las células mononucleares de sangre periférica del 20% de los pacientes con sarcoma de Kaposi. Todos los pacientes pertenecían al grupo de "altó riesgo", y eran varones homosexuales. Ninguno recibió transfusiones sanguíneas. Estos datos preliminares sugieren que la prevalencia del virus herpes humano 8 en las células mononucleares de sangre periférica de los pacientes con la infección por el virus de inmunodeficiencia humana con/sin sarcoma de Kaposi es probablemente baja en comparación con pacientes provenientes de Estados Unidos y Europa

The nucleic acid of human herpes virus 8 is present in the peripheral blood mononuclear cells of between 50% and 90% of Kaposi sarcoma patients, 7% and 10% of human immunodeficiency virus infected patients without Kaposi sarcoma. We studied the prevalence of human herpes virus 8 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection with/without Koposi sarcoma. Seventy-six patients with human immunodeficiency virus infection without Kaposi sarcoma associated with human immunodeficiency virus infection were included. Desoxibonucleico acid was extracted from the sample by a standard phenol/chloroform extraction procedure. Desoxirribonucleico acid was polimerase chain reaction amplified using Kaposi sarcoma 1 and Kaposi sarcoma 2 primers specific for the human herpes virus 8 ORF26. Polimerase chain reaction were considered positive only if the polimerase chain reaction products hybridized in the expected 233 by region. None of human immunodeficiency virus infected patients showed the presence of human herpes virus 8 in the peripheral blood mononuclear cells, and after a follow-up of 2 years, none has developed Kaposi sarcoma. Human herpes virus 8 was detected in the peripheral blood mononuclear cells from 20% of patients with Kaposi sarcoma. All patients belonged to a "high risk group", were male and homosexuals. None received blood transfusion. These preliminary data suggest that the prevalence of human herpes virus 8 in peripheral blood mononuclear cells from human immunodeficiency virus infected patients with/withoul Kaposi sarcoma is probably low in comparison with patients from EE.UU and Europe

Clinicopathological Characteristics of Kaposi's Sarcoma and Usefulness of Detection of Human Herpes Virus 8 / 대한피부과학회지

BACKGROUND: Kaposi's sarcoma (KS) is a multicentric proliferative vascular tumor which involves cutaneous and visceral tissues. Recent study has clearly identified human herpes virus 8 (HHV8) in all Kaposi's sarcoma patients, indicating that HHV8 is closely involved in the pathogenesis of Kaposi's sarcoma. OBJECTIVE: The purpose of this study was to document clinical and histopathological features of KS and to emphasize the necessity of detection of HHV8 in the differential diagnosis of KS from other vascular lesions. METHODS: The medical records and histopathological slides of patients with KS diagnosed at Ajou University Hospital from January 1995 to December 2004 were reviewed. We performed immunohistochemical stain and polymerase chain reaction (PCR)-based analysis to detect HHV8 in KS and other vascular lesions. RESULTS: Among 12 patients, classic KS was found in 9 patients, AIDS-associated KS in 1 patient, and iatrogenic immunosuppressive KS in 2 patients. Patients with KS presented with various clinical features, showing purple- colored macules to nodules or tumors. Although lower extremities are most frequently involved sites, involvement of other sites such as arm and neck was noticed. Mucosal and systemic involvement was detected in AIDS- associated case. Immunohistochemical stains for HHV8 were positive in all KS, but they were negative in other vascular lesions. PCRs for HHV8 were positive in 8 of 11 (72.7%) KS, but they were negative in other vascular lesions. Classic KS responded well to surgical and radiation therapies and showed indolent course. Immunosuppressive KS regressed partially after dose reduction of immunosuppressive drug therapy, but the lesions persisted. CONCLUSION: Immunohistochemical stain and/or PCR for HHV8 are useful means to differentiate KS from other vascular tumors.

Clinico-pathologic Study and Detection of Human Herpesvirus 8 sequence of Kaposi's Sarcoma in Korea / 대한피부과학회지

BACKGROUND: Kaposi's sarcoma (KS) is a vascular neoplasm that was rarely seen before the AIDS and transplantation era. The isolation of human herpesvirus 8 (HHV-8) in all forms of KS strongly suggests a role of this agent in the pathogenesis. OBJECTIVE: The purpose of this study was to evaluate the clinical and histopathological features of KS and assess the presence of HHV-8 sequences in Korea. METHODS: The medical records and histopathologic slides of patients with KS, who were diagnosed at Asan Medical Center from 1989 to 2005, were reviewed. We also performed polymerase chain reaction (PCR) to find out the presence of HHV-8. RESULTS: 1.Among the 22 patients, classic KS was found in 9 and iatrogenic immunosuppressive-associated KS in 13 patients. 2.Clinical features were varied, usually limiting to the skin of the extremities, however, involvement of internal organs and mucosa was also detected. 3. The histology of cutaneous lesions associated with various clinical forms of KS was essentially identical, however, it presented different features according to their stage. 4. HHV-8 sequences were identified in all cases of KS, including the lesions of internal organs. 5.Classic KS responded well to radiation therapy, thalidomide or chemotherapy, except 2 patients. Iatrogenic immunosuppressive KS improved generally after radiation therapy, IFN-alpha, or chemotherapy, but some of the patients died due to underlying diseases. CONCLUSION: KS is a rare vascular neoplasm. We retrospectively studied twenty-two cases, and HHV-8 were detected in all cases, these supporting HHV-8 as the causative agent.