title: Epstein-barr virus infection of monocytoid B-cell proliferates: an early feature of primary viral infection?
abstract: Monocytoid cells are a subset of B lymphocytes with characteristic morphology and immunophenotype, which proliferate in a broad variety of reactive lymph node conditions. Up to now, no direct infection of these cells by a pathogenic organism has been identified. We found in a series of lymph node specimens from 13 patients having in common a prominent monocytoid B (MCB)-cell reaction in the absence of epithelioid cells or necrosis evidence that Epstein-Barr virus (EBV) can infect MCB cells. Clinical and serologic findings indicative for an acute EBV infection were reported only in 2 cases. By in situ hybridization and immunohistology, a number of MCB cells in all cases was found to contain EBV-encoded small nuclear RNAs and to express the EBV-encoded nuclear antigen (EBNA)-2 and, in lesser extent, the latent membrane protein-1. EBV-transcripts and proteins were also detectable in a number of extrafollicular B blasts and germinal center B cells in 10 of 13 cases. Our findings imply that an EBV infection of MCB cells associated with predominant EBNA-2 expression represents an early sign of primary infection and that it should be included in the differential diagnosis of activated lymph nodes with prominent MCB-cell reaction in the absence of epithelioid cells.
authors.affiliation: Consultation and Reference Center for Hematopathology at the Institute of Pathology, Charité, Campus Benjamin Franklin, Medical University, Berlin, Germany. Ioannis.Anagnostopoulos@charite.de
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Korinna
authors.initials: K
authors.lastname: Joehrens
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000032:analysis; D003937:Diagnosis, Differential; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000473:pathology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000032:analysis / Q000235:genetics; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000209:etiology; D008223:Lymphoma / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D015534:Trans-Activators / Q000032:analysis; D014763:Viral Matrix Proteins / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins