Objective: To study the evolution of Kaposi‚s sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 in Europe and Africa. Design and methods: PCR and sequence analysis of the variable viral membrane glycoprotein gene K1 in 58 tumour and peripheral blood samples from patients with AIDS-related Kaposi‚s sarcoma (KS), ‚classic‚ (HIV-negative) KS, transplant KS, Multicentric Castleman‚s Disease, other lymphoproliferative disorders, and healthy KSHV-infected individuals from the UK, Denmark, Sweden, Italy, Spain, Iceland, The Faroe Islands, Greece, The Gambia and Uganda. Results: Three major groups of K1 sequences were found: A, B and C, as defined previously. The K1 gene has evolved, both within and between these three groups, under positive selection. KSHV group B strains predominate in Africa and are more distant from groups A and C, found in Europe, than A and C are from each other. Within group C two subgroups, C′ and C′′, can be identified. Subgroup C′′ is more closely related to group A in a region of the K1 protein and appears to be phylogenetically close to the branchpoint between A and C. Group A and C strains are currently found in both HIV-1-infected and -uninfected Europeans, and were already present in Europe before the start of the AIDS epidemic. We found some examples of closely related K1 sequences in Italy and Denmark, but in general KSHV strains in Europe did not cluster geographically. Conclusion: KSHV strains in East and West Africa are closely related but phylogenetically distant from those in Europe. The two major KSHV groups in Europe are more closely related, with some strains adopting an intermediate phylogenetic position. In Europe, KSHV strains may have been disseminated at least several decades ago. Variability in the K1 region is driven by selection and does not correlate with different KSHV-related pathologies or geographic regions where clinically more aggressive HIV-negative KS (‚endemic‚ KS) is more common.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are myofibroblastic lesions with unpredictable biologic behavior that occur at a young age. For this report, the authors investigated clinicopathologic features in a series of pediatric IMTs. The objective of the study was to identify morphologic or immunohistochemical prognostic markers and the possible pathogenic role of human herpes virus 8 (HHV‐8).METHODS: Twenty‐six patients were observed over a period of 18 years. Clinical/histologic data were reviewed, and immunohistochemical/molecular studies were performed.RESULTS: Patients ages 8‒216 months (median age, 60 months) presented with tumors of the lung‐bronchus (8 patients), abdomen (17 patients), and thoracic wall (1 patient). Twenty‐one patients underwent complete excision, and microscopic or macroscopic residual disease was present in 5 of those patients. Chemotherapy was received by 5 patients. After a median follow‐up of 6.6 years, 24 patients were in complete remission, and 2 patients had died of disease. Local recurrences were observed in 6 patients (including 4 recurrences that occurred after a complete excision). Cytologic atypia, low inflammatory infiltrate, and a rich myxoid pattern were detected in patients who had recurrent disease or a poor prognosis. Anaplastic lymphoma kinase (ALK) was positive in 7 patients (including 2 patients with recurrent disease). No correlation between clusterin expression and prognosis was demonstrated. HHV‐8 was identified in 1 pulmonary IMT.CONCLUSIONS: IMTs are locally aggressive lesions. In this series, the local recurrence rate was 23%, and the 5‐year and 10‐year event‐free survival rates were 87.4% and 72.8%, respectively. The results indicated that the treatment of choice is a complete, nonmutilating excision; chemotherapy may be given to patients who have microscopic or macroscopic residual disease, although the results are controversial; cytologic atypia and positive ALK status are more frequent in aggressive tumors, whereas metastatic tumors are negative for ALK; and HHV8 is not involved in the pathogenesis of IMT. Cancer 2010. © 2010 American Cancer Society.

Background: Kaposi's sarcoma (KS) is the most common cancer seen in subjects with acquired immunodeficiency syndrome (AIDS). KS etiology and pathogenesis are still ill defined, and no definite improvement in survival has been obtained with current chemotherapeutic regimens. This open prospective study was aimed at evaluating the clinical response of AIDS-related KS to highly active antiretroviral therapy (HAART), a combination of protease and reverse transcriptase inhibitors, as well as the relationship between clinical response, human immunodeficiency virus type 1 (HIV-1) burden, and antibody titer against human herpesvirus 8 (HHV8) proteins. Patients and Methods: Fourteen KS patients were studied; 12 were in the poor-risk group. At given intervals, the patients underwent clinical examination, and their CD4⁺ cell counts, plasma HIV-1 RNA levels, and antibody titers to lytic-phase ORF65 and latent-phase HHV8 proteins were determined. Results: When last seen, the overall clinical response rate was 86% (median follow-up, 22 months); 10 complete and two partial responses were achieved, and two patients showed disease progression. All patients with complete or partial response showed a consistent decrease in HIV-1 RNA levels, with a corresponding increase in CD4⁺ cell counts; HIV-1 RNA levels in the two progressors remained persistently high, despite a change in HAART. HHV8 ORF65 antibody titers were generally higher in patients with extensive skin or mucosal/visceral involvement versus patients with limited disease; no differences in latent-phase HHV8 antibody titers were observed in relation to tumor burden. Conclusion: The findings indicate that antiretroviral therapy with protease inhibitors is effective for AIDS-related KS; the clinical response was correlated with a decrease in plasma HIV-1 RNA levels and an increase in CD4⁺ lymphocytes, whereas antibody levels to the lytic-phase HHV8 protein were influenced by the extent of tumor involvement.