title: KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder: New Findings and Review of the Literature.
abstract: We report 2 cases of Kaposi sarcoma-associated herpesvirus (KSHV)-and Epstein-Barr Virus (EBV) associated germinotropic lymphoproliferative disorder. Both cases arose in patients from regions endemic for KSHV, Cape Verde, and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of human herpesvirus 8 (HHV-8) positive multicentric Castleman disease. The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral interleukin 6, as well as Epstein-Barr virus-encoded small RNA by in situ hybridization. They showed a latency I phenotype, being negative for LMP1, EBNA2, and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in 1 case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. Germinotropic lymphoproliferative disorder is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral interleukin 6 and provide evidence for latency I phenotype for EBV. In addition, 1 case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.
authors.affiliation: *Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD †Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA ‡Department of Pathology, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Tapan
authors.initials: T
authors.lastname: Bhavsar
authors.forename: John C
authors.initials: JC
authors.lastname: Lee
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Perner
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006566:Herpesviridae Infections / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers