title: Lymph node-based disease and HHV-8/KSHV infection in HIV seronegative patients: report of three new cases of a heterogeneous group of diseases.
abstract: 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-1 of 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.
authors.affiliation: Unit of Pathologic Anatomy and Oncology, A.O. "San Giovanni di Dio e Ruggi d'Aragona", via S. Leonardo, Salerno, Italy. ada66@inwind.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Antonio
authors.affiliation: Unit of Pathologic Anatomy, Hospital "Scarlato", ASL SA1, Scafati (SA), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Addesso
authors.affiliation: Unit of Pathologic Anatomy and Oncology, A.O. "San Giovanni di Dio e Ruggi d'Aragona", via S. Leonardo, Salerno, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Memoli
authors.affiliation: Unit Pathologic Anatomy, National Tumor Institute "Pascale", Naples, Italy.
authors.forename: Pina
authors.initials: P
authors.lastname: Liguori
authors.affiliation: University of Medicine, Salerno, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cuomo
authors.affiliation: Unit of Pathologic Anatomy, A.O.R.N. Hospital "Cardarelli", Naples, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Boscaino
authors.affiliation: Unit of Pathologic Anatomy, A.O.R.N. Hospital "Cardarelli", Naples, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Nappi
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018023:HIV Seronegativity; D006566:Herpesviridae Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis