Lymph node-based disease and HHV-8/KSHV infection in HIV seronegative patients: report of three new cases of a heterogeneous group of diseases

• Published in: International journal of hematology 2011-06, Vol.93 (6), p.795-801
• Main Authors: D’Antonio, Antonio, Addesso, Maria, Memoli, Domenico, Liguori, Pina, Cuomo, Roberto, Boscaino, Amedeo, Nappi, Oscar
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Case Report; Female; Hematologic and hematopoietic diseases; Hematology; Herpesviridae Infections - complications; Herpesviridae Infections - metabolism; Herpesviridae Infections - pathology; Herpesviridae Infections - virology; Herpesvirus 4, Human - genetics; Herpesvirus 8, Human - physiology; HIV Seronegativity; Human viral diseases; Humans; Immunophenotyping; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphoma, Large B-Cell, Diffuse - complications; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoproliferative Disorders - complications; Lymphoproliferative Disorders - metabolism; Lymphoproliferative Disorders - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Plasma Cells - metabolism; Plasma Cells - pathology; Prognosis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-011-0849-0

We describe three cases of lymph proliferative diseases characterized by the presence of lymphoma cells expressing the KSHV/HHV-8 antigen with or without EBV expression. The patients were HIV seronegative without serous effusions. One case was diagnosed as KSHV-germinotropic lymphoproliferative disorder due to the presence of atypical plasmablasts involving germinal centers. These plasmablasts were positive for MUM1 and vIL6, co-expressed EBV and LNA-1of HHV-8/KSHV, and showed a polyclonal pattern of Ig gene rearrangements on PCR. The disease was localized and the prognosis was good. In two other cases, a diagnosis of KSHV/HHV-8-related diffuse large cell B-lymphoma morphology was made. The lymphoma cells were anaplastic or frankly pleomorphic, expressed KSHV but not EBV, and were positive for CD20, MUM1, PAX-5, and vIL6. In both cases the prognosis was poor. On the basis of the features observed, we raise three considerations: (1) KSHV-related lymphoproliferative disorders represent a distinctive and heterogeneous group of diseases with variable clinico-pathologic findings and immunophenotypes (BCL6−/MUM1+/CD138− and BCL6+/MUM1+/CD138− or BCL6−/MUM1+/CD138+). (2) Although the pathogenic mechanism of HHV8 in lymphomagenesis is unclear, the presence the viral DNA in lymph nodes of HIV− patients is not a simply opportunistic infection, but is directly implicated in the pathogenesis of KSHV-related diseases; the activation of IL-6 receptor signalling may play an important role in most cases. (3) The different prognoses among different diseases with KSHV etiology may be related to the fact that the pathogenic potential appears to be constrained by a competent immune system.