title: KSHV- and EBV-associated germinotropic lymphoproliferative disorder.
abstract: Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic kappa or lambda light chain. Clusters of CD10(+)CD20(+) residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity "KSHV-associated germinotropic lymphoproliferative disorder."
authors.affiliation: Department of Histopathology, Royal Free and University College Medical School, University College London, Rockefeller Building, University Street, London WC1E 6JJ, UK. m.du@ucl.ac.uk
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
authors.forename: Tim C
authors.initials: TC
authors.lastname: Diss
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Rifat A
authors.initials: RA
authors.lastname: Hamoudi
authors.forename: José
authors.initials: J
authors.lastname: Cabeçadas
authors.forename: Henry Y
authors.initials: HY
authors.lastname: Dong
authors.forename: Nancy Lee
authors.initials: NL
authors.lastname: Harris
authors.forename: John K C
authors.initials: JK
authors.lastname: Chan
authors.forename: John W
authors.initials: JW
authors.lastname: Rees
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Peter G
authors.initials: PG
authors.lastname: Isaacson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001706:Biopsy; D002999:Clone Cells / Q000737:chemistry / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D018858:Germinal Center / Q000473:pathology; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D019288:Herpesvirus 8, Human / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D016130:Immunophenotyping; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000532:radiotherapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D011241:Prednisone / Q000008:administration & dosage; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone